[Expressions of Ras and Sos1 in epithelial ovarian cancer tissues and their clinical significance].

Science.gov (United States)

Xiao, Zheng-Hua; Linghu, Hua; Liu, Qian-Fen

2016-11-20

To detect the expressions of Ras and Sos1 proteins in human epithelial ovarian cancer (EOC) tissues and explore their correlation with the clinicopathological features of the patients. The expressions of Ras and Sos1 proteins were detected immunohistochemically in 62 EOC tissues, 5 borderline ovarian cancer tissues, 15 benign epithelial ovarian neoplasm tissues, and 18 normal ovarian tissues. The EOC tissues showed significantly higher expression levels of both Ras and Sos1 than the other tissues tested (Ptissues, Ras and Sos1 proteins were expressed mostly on the cell membrane and in the cytoplasm. The expression level of Ras was correlated with pathological types of the tumor (Ptissue-specific variation of Ras expression can lend support to a specific diagnosis of ovarian serous adenocarcinoma. The association of Ras and Sos1 protein expression with the tumor-free survival time of the patients awaits further investigation with a larger sample size.

The SOS Chromotest applied for screening plant antigenotoxic agents against ultraviolet radiation.

Science.gov (United States)

Fuentes, J L; García Forero, A; Quintero Ruiz, N; Prada Medina, C A; Rey Castellanos, N; Franco Niño, D A; Contreras García, D A; Córdoba Campo, Y; Stashenko, E E

2017-09-13

In this work, we investigated the usefulness of the SOS Chromotest for screening plant antigenotoxic agents against ultraviolet radiation (UV). Fifty Colombian plant extracts obtained by supercritical fluid (CO 2 ) extraction, twelve plant extract constituents (apigenin, carvacrol, β-caryophyllene, 1,8-cineole, citral, p-cymene, geraniol, naringenin, pinocembrin, quercetin, squalene, and thymol) and five standard antioxidant and/or photoprotective agents (curcumin, epigallocatechin gallate, resveratrol, α-tocopherol, and Trolox®) were evaluated for their genotoxicity and antigenotoxicity against UV using the SOS Chromotest. None of the plant extracts, constituents or agents were genotoxic in the SOS Chromotest at tested concentrations. Based on the minimal extract concentration that significantly inhibited UV-genotoxicity (CIG), five plant extracts were antigenotoxic against UV as follows: Baccharis nítida (16 μg mL -1 ) = Solanum crotonifolium (16 μg mL -1 ) > Hyptis suaveolens (31 μg mL -1 ) = Persea caerulea (31 μg mL -1 ) > Lippia origanoides (62 μg mL -1 ). Based on CIG values, the flavonoid compounds showed the highest antigenotoxic potential as follows: apigenin (7 μM) > pinocembrin (15 μM) > quercetin (26 μM) > naringenin (38 μM) > epigallocatechin gallate (108 μM) > resveratrol (642 μM). UV-genotoxicity inhibition with epigallocatechin gallate, naringenin and resveratrol was related to its capability for inhibiting protein synthesis. A correlation analysis between compound antigenotoxicity estimates and antioxidant activity evaluated by the oxygen radical absorbance capacity (ORAC) assay showed that these activities were not related. The usefulness of the SOS Chromotest for bioprospecting of plant antigenotoxic agents against UV was discussed.

Nash-Williams’ cycle-decomposition theorem

DEFF Research Database (Denmark)

Thomassen, Carsten

2016-01-01

We give an elementary proof of the theorem of Nash-Williams that a graph has an edge-decomposition into cycles if and only if it does not contain an odd cut. We also prove that every bridgeless graph has a collection of cycles covering each edge at least once and at most 7 times. The two results...

Quinolone Resistance Reversion by Targeting the SOS Response

Directory of Open Access Journals (Sweden)

E. Recacha

2017-10-01

Full Text Available Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs and dynamic (killing curves or flow cytometry methodologies. A peritoneal sepsis murine model was used to evaluate in vivo impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs. Killing curve assays showed a clear disadvantage for survival (Δlog10 CFU per milliliter [CFU/ml] of 8 log units after 24 h, and the in vivo efficacy of ciprofloxacin was significantly enhanced (Δlog10 CFU/g of 1.76 log units in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of E. coli phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the in vivo efficacy.

The investigation of SOS-response of Escherichia coli after γ-irradiation by means of SOS-chromotest

International Nuclear Information System (INIS)

Kozubek, S.; Ogievetskaya, M.M.; Krasavin, E.A.; Drasil, V.; Soska, J.

1988-01-01

The kinetics of the E.coli PQ37 SOS-system induction by γ-radiation has been studied by the SOS-chromotest technique. The experimental data are consistent with the following hypotheses. The production of DNA damages inducing the SOS-system is 0,021 Gy -1 per genome. The SOS-system is switched off approximately 200 min after γ-irradiation. The spontaneous triggering of the SOS-system is induced in the exponentially growing cells. The probability of its induction is independent of time up to 180 min of incubation. The synthesis of constitutive alkaline phosphatase proceeds for some time in the cells that suffered lethal damages from γ-irradiation. A correction has been proposed for the calculation of the induction factor. 5 refs.; 11 figs

Genetic characterization of the inducible SOS-like system of Bacillus subtilis

Energy Technology Data Exchange (ETDEWEB)

Love, P.E.; Yasbin, R.E.

1984-12-01

The SOS-like system of Bacillus subtilis consists of several coordinately induced phenomena which are expressed after cellular insult such as DNA damage of inhibition of DNA replication. Mutagenesis of the bacterial chromosomes and the development of maintenance of competence also appear to be involved in the SOS-like response in this bacterium. The genetic characterization of the SOS-like system has involved an analysis of (i) the effects of various DNA repair mutations on the expression of inducible phenomena and (ii) the tsi-23 mutation, which renders host strains thermally inducible for each of the SOS-like functions. Bacterial filamentation was unaffected by any of the DNA repair mutations studied. In contrast, the induction of prophage after thermal or UV pretreatment was abolished in strains carrying the recE4, recA1, recB2, or recG13 mutation. The Weigle reactivation of UV-damaged bacteriophage was also inhibited by the recE4, recA1, recB2, or recG13 mutation, whereas levels of Weigle reactivation were lower in strains which carried the uvrA42, polA5, or rec-961 mutation than in the DNA repair-proficient strain. Strains which carried the recE4 mutation were incapable of chromosomal DNA-mediated transformation, and the frequency of this event was decreased in strains carrying recA1, recB2, or tsi-23 mutation. Plasmid DNA transformation efficiency was decreased only in strains carrying the tsi-23 mutation in addition to the recE4, recA1, or recB2 mutation. The results indicate that the SOS-like system of B. subtilis is regulated at different levels by two or more gene products. In this report, the current data regarding the genetic regulation of inducible phenomena are summarized, and a model is proposed to explain the mechanism of SOS-like induction in B. subtillis. 50 references, 3 figures, 6 tables.

A Modular SOS for Action Notation - Revisited

DEFF Research Database (Denmark)

Mosses, Peter David

A draft modular SOS for the new version of AN, referred to as AN-2, has been available since 2000. It is written in CASL and has been checked for well-formedness using CATS (CASL Tool Set). It appears to be significantly more accessible than the original SOS of AN-1. However, it now appears......-notation for the modular SOS rules. After discussing the issues, we look at some illustrative examples taken from an improved modular SOS of AN-2 (in preparation). We also look at the possibility of empirical testing of the modular SOS by a straightforward translation to Prolog....

Molecular Pathogenesis of NASH

Directory of Open Access Journals (Sweden)

Alessandra Caligiuri

2016-09-01

Full Text Available Nonalcoholic steatohepatitis (NASH is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression.

[SOS-repair--60 years].

Science.gov (United States)

Zavil'gel'skiĭ, G B

2013-01-01

This review integrates 60 years of research on SOS-repair and SOS-mutagenesis in procaryotes and eucaryotes, from Jean Weigle experiment in 1953 year (mutagenesis of lambda bacteriophage in UV-irradiated bacteria) to the latest achievements in studying SOS-mutagenesis on all living organisms--Eukarya, Archaea and Bacteria. A key role in establishing of a biochemical basis for SOS-mutagenesis belonges to the finding in 1998-1999 years that specific error-prone DNA polymerases (PolV and others) catalysed translesion synthesis on damaged DNA. This review focuses on recent studies addressing the new models for SOS-induced mutagenesis in Escherichia coli and Home sapiens cells.

Non-commutative Nash inequalities

International Nuclear Information System (INIS)

Kastoryano, Michael; Temme, Kristan

2016-01-01

A set of functional inequalities—called Nash inequalities—are introduced and analyzed in the context of quantum Markov process mixing. The basic theory of Nash inequalities is extended to the setting of non-commutative L p spaces, where their relationship to Poincaré and log-Sobolev inequalities is fleshed out. We prove Nash inequalities for a number of unital reversible semigroups

NOAA NDBC SOS - waves

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NDBC SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have waves data. Because of the nature of SOS requests, requests for data...

Quinolone Resistance Reversion by Targeting the SOS Response.

Science.gov (United States)

Recacha, E; Machuca, J; Díaz de Alba, P; Ramos-Güelfo, M; Docobo-Pérez, F; Rodriguez-Beltrán, J; Blázquez, J; Pascual, A; Rodríguez-Martínez, J M

2017-10-10

Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine model was used to evaluate in vivo impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve assays showed a clear disadvantage for survival (Δlog 10 CFU per milliliter [CFU/ml] of 8 log units after 24 h), and the in vivo efficacy of ciprofloxacin was significantly enhanced (Δlog 10 CFU/g of 1.76 log units) in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min) of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of E. coli phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the in vivo efficacy. IMPORTANCE The rapid rise of antibiotic resistance in bacterial pathogens is now considered a major global health crisis. New strategies are needed to block the development of resistance and to extend the life of antibiotics. The SOS response is a promising target for developing therapeutics to reduce the acquisition of antibiotic resistance and enhance the bactericidal activity of antimicrobial agents such as quinolones. Significant questions remain regarding its impact as a strategy for the reversion or resensitization of antibiotic-resistant bacteria. To address this

Reconstitution in yeast of the Arabidopsis SOS signaling pathway for Na+ homeostasis

OpenAIRE

Quintero, Francisco J.; Ohta, Masaru; Shi, Huazhong; Zhu, Jian-Kang; Pardo, José M.

2002-01-01

The Arabidopsis thaliana SOS1 protein is a putative Na H antiporter that functions in Na extrusion and is essential for the NaCl tolerance of plants. sos1 mutant plants share phenotypic similarities with mutants lacking the protein kinase SOS2 and the Ca2 sensor SOS3. To investigate whether the three SOS proteins function in the same response pathway, we have reconstituted the SOS system in yeast cells. Expression of SOS1 improved the Na tolerance of yeast mutants la...

SoS contract verification using statistical model checking

Directory of Open Access Journals (Sweden)

Alessandro Mignogna

2013-11-01

Full Text Available Exhaustive formal verification for systems of systems (SoS is impractical and cannot be applied on a large scale. In this paper we propose to use statistical model checking for efficient verification of SoS. We address three relevant aspects for systems of systems: 1 the model of the SoS, which includes stochastic aspects; 2 the formalization of the SoS requirements in the form of contracts; 3 the tool-chain to support statistical model checking for SoS. We adapt the SMC technique for application to heterogeneous SoS. We extend the UPDM/SysML specification language to express the SoS requirements that the implemented strategies over the SoS must satisfy. The requirements are specified with a new contract language specifically designed for SoS, targeting a high-level English- pattern language, but relying on an accurate semantics given by the standard temporal logics. The contracts are verified against the UPDM/SysML specification using the Statistical Model Checker (SMC PLASMA combined with the simulation engine DESYRE, which integrates heterogeneous behavioral models through the functional mock-up interface (FMI standard. The tool-chain allows computing an estimation of the satisfiability of the contracts by the SoS. The results help the system architect to trade-off different solutions to guide the evolution of the SoS.

Sequence analysis of the Ras-MAPK pathway genes SOS1, EGFR & GRB2 in silver foxes (Vulpes vulpes): candidate genes for hereditary hyperplastic gingivitis.

Science.gov (United States)

Clark, Jo-Anna B J; Tully, Sara J; Dawn Marshall, H

2014-12-01

Hereditary hyperplastic gingivitis (HHG) is an autosomal recessive disease that presents with progressive gingival proliferation in farmed silver foxes. Hereditary gingival fibromatosis (HGF) is an analogous condition in humans that is genetically heterogeneous with several known autosomal dominant loci. For one locus the causative mutation is in the Son of sevenless homologue 1 (SOS1) gene. For the remaining loci, the molecular mechanisms are unknown but Ras pathway involvement is suspected. Here we compare sequences for the SOS1 gene, and two adjacent genes in the Ras pathway, growth receptor bound protein 2 (GRB2) and epidermal growth factor receptor (EGFR), between HHG-affected and unaffected foxes. We conclude that the known HGF causative mutation does not cause HHG in foxes, nor do the coding regions or intron-exon boundaries of these three genes contain any candidate mutations for fox gum disease. Patterns of molecular evolution among foxes and other mammals reflect high conservation and strong functional constraints for SOS1 and GRB2 but reveal a lineage-specific pattern of variability in EGFR consistent with mutational rate differences, relaxed functional constraints, and possibly positive selection.

Effect of the SOS response on the mean fitness of unicellular populations: a quasispecies approach.

Science.gov (United States)

Kama, Amit; Tannenbaum, Emmanuel

2010-11-30

The goal of this paper is to develop a mathematical model that analyzes the selective advantage of the SOS response in unicellular organisms. To this end, this paper develops a quasispecies model that incorporates the SOS response. We consider a unicellular, asexually replicating population of organisms, whose genomes consist of a single, double-stranded DNA molecule, i.e. one chromosome. We assume that repair of post-replication mismatched base-pairs occurs with probability , and that the SOS response is triggered when the total number of mismatched base-pairs is at least . We further assume that the per-mismatch SOS elimination rate is characterized by a first-order rate constant . For a single fitness peak landscape where the master genome can sustain up to mismatches and remain viable, this model is analytically solvable in the limit of infinite sequence length. The results, which are confirmed by stochastic simulations, indicate that the SOS response does indeed confer a fitness advantage to a population, provided that it is only activated when DNA damage is so extensive that a cell will die if it does not attempt to repair its DNA.

Escherichia coli DinB inhibits replication fork progression without significantly inducing the SOS response.

Science.gov (United States)

Mori, Tetsuya; Nakamura, Tatsuro; Okazaki, Naoto; Furukohri, Asako; Maki, Hisaji; Akiyama, Masahiro Tatsumi

2012-01-01

The SOS response is readily triggered by replication fork stalling caused by DNA damage or a dysfunctional replicative apparatus in Escherichia coli cells. E. coli dinB encodes DinB DNA polymerase and its expression is upregulated during the SOS response. DinB catalyzes translesion DNA synthesis in place of a replicative DNA polymerase III that is stalled at a DNA lesion. We showed previously that DNA replication was suppressed without exogenous DNA damage in cells overproducing DinB. In this report, we confirm that this was due to a dose-dependent inhibition of ongoing replication forks by DinB. Interestingly, the DinB-overproducing cells did not significantly induce the SOS response even though DNA replication was perturbed. RecA protein is activated by forming a nucleoprotein filament with single-stranded DNA, which leads to the onset of the SOS response. In the DinB-overproducing cells, RecA was not activated to induce the SOS response. However, the SOS response was observed after heat-inducible activation in strain recA441 (encoding a temperature-sensitive RecA) and after replication blockage in strain dnaE486 (encoding a temperature-sensitive catalytic subunit of the replicative DNA polymerase III) at a non-permissive temperature when DinB was overproduced in these cells. Furthermore, since catalytically inactive DinB could avoid the SOS response to a DinB-promoted fork block, it is unlikely that overproduced DinB takes control of primer extension and thus limits single-stranded DNA. These observations suggest that DinB possesses a feature that suppresses DNA replication but does not abolish the cell's capacity to induce the SOS response. We conclude that DinB impedes replication fork progression in a way that does not activate RecA, in contrast to obstructive DNA lesions and dysfunctional replication machinery.

A plasmid-encoded UmuD homologue regulates expression of Pseudomonas aeruginosa SOS genes.

Science.gov (United States)

Díaz-Magaña, Amada; Alva-Murillo, Nayeli; Chávez-Moctezuma, Martha P; López-Meza, Joel E; Ramírez-Díaz, Martha I; Cervantes, Carlos

2015-07-01

The Pseudomonas aeruginosa plasmid pUM505 contains the umuDC operon that encodes proteins similar to error-prone repair DNA polymerase V. The umuC gene appears to be truncated and its product is probably not functional. The umuD gene, renamed umuDpR, possesses an SOS box overlapped with a Sigma factor 70 type promoter; accordingly, transcriptional fusions revealed that the umuDpR gene promoter is activated by mitomycin C. The predicted sequence of the UmuDpR protein displays 23 % identity with the Ps. aeruginosa SOS-response LexA repressor. The umuDpR gene caused increased MMC sensitivity when transferred to the Ps. aeruginosa PAO1 strain. As expected, PAO1-derived knockout lexA-  mutant PW6037 showed resistance to MMC; however, when the umuDpR gene was transferred to PW6037, MMC resistance level was reduced. These data suggested that UmuDpR represses the expression of SOS genes, as LexA does. To test whether UmuDpR exerts regulatory functions, expression of PAO1 SOS genes was evaluated by reverse transcription quantitative PCR assays in the lexA-  mutant with or without the pUC_umuD recombinant plasmid. Expression of lexA, imuA and recA genes increased 3.4-5.3 times in the lexA-  mutant, relative to transcription of the corresponding genes in the lexA+ strain, but decreased significantly in the lexA- /umuDpR transformant. These results confirmed that the UmuDpR protein is a repressor of Ps. aeruginosa SOS genes controlled by LexA. Electrophoretic mobility shift assays, however, did not show binding of UmuDpR to 5' regions of SOS genes, suggesting an indirect mechanism of regulation.

49 CFR 40.99 - How long does the laboratory retain specimens after testing?

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false How long does the laboratory retain specimens after testing? 40.99 Section 40.99 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Drug Testing Laboratories § 40.99 How...

Evelin Ilves avas SOS Lasteküla

Index Scriptorium Estoniae

2010-01-01

SOS Lasteküla patroon proua Evelin Ilves avas 1. juunil 2010 Põltsamaal Eesti teise SOS Lasteküla. Presidendi abikaasa tõi kingiks õunapuuistikuid ja lasteraamatuid. Ilmunud ka: Eesti Päevaleht 2. juuni 2010, lk. 4

[SOS response of DNA repair and genetic cell instability under hypoxic conditions].

Science.gov (United States)

Vasil'eva, S V; Strel'tsova, D A

2011-01-01

The SOS DNA repair pathway is induced in E. coli as a multifunctional cell response to a wide variety of signals: UV, X or gamma-irradiation, mitomycin C or nalidixic acid treatment, thymine starvation, etc. Triggering of the system can be used as a general and early sign of DNA damage. Additionally, the SOS-response is known to be an "error-prone" DNA repair pathway and one of the sources of genetic instability. Hypoxic conditions are established to be the major factor of genetic instability as well. In this paper we for the first time studied the SOS DNA repair response under hypoxic conditions induced by the well known aerobic SOS-inducers. The SOS DNA repair response was examined as a reaction of E. coli PQ37 [sfiA::lacZ] cells to UVC, NO-donating agents and 4NQO. Here we provide evidence that those agents were able to induce the SOS DNA repair response in E. coli at anaerobic growth conditions. The process does not depend on the transcriptional activity of the universal protein of E. col anaerobic growth Fnr [4Fe-4S]2+ or can not be referred to as an indicator of genetic instability in hypoxic conditions.

Vesiculation from Pseudomonas aeruginosa under SOS.

Science.gov (United States)

Maredia, Reshma; Devineni, Navya; Lentz, Peter; Dallo, Shatha F; Yu, Jiehjuen; Guentzel, Neal; Chambers, James; Arulanandam, Bernard; Haskins, William E; Weitao, Tao

2012-01-01

Bacterial infections can be aggravated by antibiotic treatment that induces SOS response and vesiculation. This leads to a hypothesis concerning association of SOS with vesiculation. To test it, we conducted multiple analyses of outer membrane vesicles (OMVs) produced from the Pseudomonas aeruginosa wild type in which SOS is induced by ciprofloxacin and from the LexA noncleavable (lexAN) strain in which SOS is repressed. The levels of OMV proteins, lipids, and cytotoxicity increased for both the treated strains, demonstrating vesiculation stimulation by the antibiotic treatment. However, the further increase was suppressed in the lexAN strains, suggesting the SOS involvement. Obviously, the stimulated vesiculation is attributed by both SOS-related and unrelated factors. OMV subproteomic analysis was performed to examine these factors, which reflected the OMV-mediated cytotoxicity and the physiology of the vesiculating cells under treatment and SOS. Thus, SOS plays a role in the vesiculation stimulation that contributes to cytotoxicity.

"Hello!" from Crosby and Nash

CERN Multimedia

CERN Bulletin

2015-01-01

On Tuesday, 29 September, American musicians David Crosby and Graham Nash visited CERN. They also recorded a video message, commenting on their visit and sending their greetings and thanks to CERN's people.   (Video: Christoph M. Madsen/CERN.) David Crosby, Graham Nash, and Stephen Stills have played together for over 30 years in the Crosby, Stills and Nash folk rock band. Originally, together with Neil Young, they were all members of the Crosby, Stills, Nash and Young band, having played at the iconic Woodstock Festival and produced many legendary songs such as Teach Your Children, Judy Blue Eyes, Our House and Marrakech Express. ​

Unexpected Cartilage Phenotype in CD4-Cre-Conditional SOS-Deficient Mice.

Science.gov (United States)

Guittard, Geoffrey; Gallardo, Devorah L; Li, Wenmei; Melis, Nicolas; Lui, Julian C; Kortum, Robert L; Shakarishvili, Nicholas G; Huh, Sunmee; Baron, Jeffrey; Weigert, Roberto; Kramer, Joshua A; Samelson, Lawrence E; Sommers, Connie L

2017-01-01

RAS signaling is central to many cellular processes and SOS proteins promote RAS activation. To investigate the role of SOS proteins in T cell biology, we crossed Sos1 f/f Sos2 -/- mice to CD4-Cre transgenic mice. We previously reported an effect of these mutations on T cell signaling and T cell migration. Unexpectedly, we observed nodules on the joints of greater than 90% of these mutant mice at 5 months of age, especially on the carpal joints. As the mice aged further, some also displayed joint stiffness, hind limb paralysis, and lameness. Histological analysis indicated that the abnormal growth in joints originated from dysplastic chondrocytes. Second harmonic generation imaging of the carpal nodules revealed that nodules were encased by rich collagen fibrous networks. Nodules formed in mice also deficient in RAG2, indicating that conventional T cells, which undergo rearrangement of the T cell antigen receptor, are not required for this phenotype. CD4-Cre expression in a subset of cells, either immune lineage cells (e.g., non-conventional T cells) or non-immune lineage cells (e.g., chondrocytes) likely mediates the dramatic phenotype observed in this study. Disruptions of genes in the RAS signaling pathway are especially likely to cause this phenotype. These results also serve as a cautionary tale to those intending to use CD4-Cre transgenic mice to specifically delete genes in conventional T cells.

A hierarchy of SOS rule formats

NARCIS (Netherlands)

Groote, J.F.; Mousavi, M.R.; Reniers, M.A.; Mosses, P.D.; Ulidowski, I.

2006-01-01

In 1981 Structural Operational Semantics (SOS) was introduced as a systematic way to define operational semantics of programming languages by a set of rules of a certain shape [G.D. Plotkin. A structural approach to operational semantics. Technical Report DAIMI FN-19, Computer Science Department,

The complex between SOS3 and SOS2 regulatory domain from Arabidopsis thaliana: cloning, expression, purification, crystallization and preliminary X-ray analysis

Energy Technology Data Exchange (ETDEWEB)

Sánchez-Barrena, María José; Moreno-Pérez, Sandra; Angulo, Iván; Martínez-Ripoll, Martín; Albert, Armando, E-mail: xalbert@iqfr.csic.es [Grupo de Cristalografía Macromolecular y Biología Estructural, Instituto de Química Física ‘Rocasolano’, Consejo Superior de Investigaciones Científicas, Serrano 119, E-28006 Madrid (Spain)

2007-07-01

Recombinant SOS3 and SOS2 regulatory domain from A. thaliana have been coexpressed in E. coli, purified and crystallized by the hanging-drop vapour-diffusion method. An X-ray data set has been collected at 2.0 Å resolution. The salt-tolerance genes SOS3 (salt overly sensitive 3) and SOS2 (salt overly sensitive 2) regulatory domain of Arabidopsis thaliana were cloned into a polycistronic plasmid and the protein complex was expressed in Escherichia coli, allowing purification to homogeneity in three chromatographic steps. Crystals were grown using vapour-diffusion techniques. The crystals belonged to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 44.14, b = 57.39, c = 141.90 Å.

Glutathione S-transferase M1-null genotype as risk factor for SOS in oxaliplatin-treated patients with metastatic colorectal cancer.

Science.gov (United States)

Vreuls, C P H; Olde Damink, S W M; Koek, G H; Winstanley, A; Wisse, E; Cloots, R H E; van den Broek, M A J; Dejong, C H C; Bosman, F T; Driessen, A

2013-02-19

Oxaliplatin is used as a neo-adjuvant therapy in hepatic colorectal carcinoma metastasis. This treatment has significant side effects, as oxaliplatin is toxic to the sinusoidal endothelial cells and can induce sinusoidal obstruction syndrome (SOS), which is related to decreased overall survival. Glutathione has an important role in the defence system, catalysed by glutathione S-transferase (GST), including two non-enzyme producing polymorphisms (GSTM1-null and GSTT1-null). We hypothesise that patients with a non-enzyme producing polymorphism have a higher risk of developing toxic injury owing to oxaliplatin. In the nontumour-bearing liver, the presence of SOS was studied histopathologically. The genotype was determined by a semi-nested PCR. Thirty-two of the 55 (58%) patients showed SOS lesions, consisting of 27% mild, 22% moderate and 9% severe lesions. The GSTM1-null genotype was present in 25 of the 55 (46%). Multivariate analysis showed that the GSTM1-null genotype significantly correlated with the presence of (moderate-severe) SOS (P=0.026). The GSTM1-null genotype is an independent risk factor for SOS. This finding allows us, in association with other risk factors, to conceive a potential risk profile predicting whether the patient is at risk of developing SOS, before starting oxaliplatin, and subsequently might result in adjustment of treatment.

 The product of triglycerides and glucose as biomarker for screening simple steatosis and NASH in asymptomatic women.

Science.gov (United States)

Simental-Mendía, Luis E; Simental-Mendía, Esteban; Rodríguez-Hernández, Heriberto; Rodríguez-Morán, Martha; Guerrero-Romero, Fernando

2016-01-01

 Introduction and aim. Given that early identification of non-alcoholic fatty liver disease (NAFLD) is an important issue for primary prevention of hepatic disease, the objectives of this study were to evaluate the efficacy of the product of triglyceride and glucose levels (TyG) for screening simple steatosis and non-alcoholic steatohepatitis (NASH) in asymptomatic women, and to compare its efficacy vs. other biomarkers for recognizing NAFLD. Asymptomatic women aged 20 to 65 years were enrolled into a cross-sectional study. The optimal values of TyG, for screening simple steatosis and NASH were established on a Receiver Operating Characteristic scatter plot; the sensitivity, specificity, and likelihood ratios of TyG index were estimated versus liver biopsy. According sensitivity and specificity, the efficacy of TyG was compared versus the well-known clinical biomarkers for recognizing NAFLD. A total of 50 asymptomatic women were enrolled. The best cutoff point of TyG for screening simple steatosis was 4.58 (sensitivity 0.94, specificity 0.69); in addition, the best cutoff point of TyG index for screening NASH was 4.59 (sensitivity 0.87, specificity 0.69). The positive and negative likelihood ratios were 3.03 and 0.08 for simple steatosis, and 2.80 and 0.18 for NASH. As compared versus SteatoTest, NashTest, Fatty liver index, and Algorithm, the TyG showed to be the best test for screening. TyG has high sensitivity and low negative likelihood ratio; as compared with other clinical biomarkers, the TyG showed to be the best test for screening simple steatosis and NASH.

The SbSOS1 gene from the extreme halophyte Salicornia brachiata enhances Na(+) loading in xylem and confers salt tolerance in transgenic tobacco.

Science.gov (United States)

Yadav, Narendra Singh; Shukla, Pushp Sheel; Jha, Anupama; Agarwal, Pradeep K; Jha, Bhavanath

2012-10-11

Soil salinity adversely affects plant growth and development and disturbs intracellular ion homeostasis resulting cellular toxicity. The Salt Overly Sensitive 1 (SOS1) gene encodes a plasma membrane Na(+)/H(+) antiporter that plays an important role in imparting salt stress tolerance to plants. Here, we report the cloning and characterisation of the SbSOS1 gene from Salicornia brachiata, an extreme halophyte. The SbSOS1 gene is 3774 bp long and encodes a protein of 1159 amino acids. SbSOS1 exhibited a greater level of constitutive expression in roots than in shoots and was further increased by salt stress. Overexpressing the S. brachiata SbSOS1 gene in tobacco conferred high salt tolerance, promoted seed germination and increased root length, shoot length, leaf area, fresh weight, dry weight, relative water content (RWC), chlorophyll, K(+)/Na(+) ratio, membrane stability index, soluble sugar, proline and amino acid content relative to wild type (WT) plants. Transgenic plants exhibited reductions in electrolyte leakage, reactive oxygen species (ROS) and MDA content in response to salt stress, which probably occurred because of reduced cytosolic Na(+) content and oxidative damage. At higher salt stress, transgenic tobacco plants exhibited reduced Na(+) content in root and leaf and higher concentrations in stem and xylem sap relative to WT, which suggests a role of SbSOS1 in Na(+) loading to xylem from root and leaf tissues. Transgenic lines also showed increased K(+) and Ca(2+) content in root tissue compared to WT, which reflect that SbSOS1 indirectly affects the other transporters activity. Overexpression of SbSOS1 in tobacco conferred a high degree of salt tolerance, enhanced plant growth and altered physiological and biochemical parameters in response to salt stress. In addition to Na(+) efflux outside the plasma membrane, SbSOS1 also helps to maintain variable Na(+) content in different organs and also affect the other transporters activity indirectly. These

Bioavailability of {sup 99m}Tc-paclitaxel-glucuronide ({sup 99m}Tc-PAC-G)

Energy Technology Data Exchange (ETDEWEB)

Biber Muftuler, F.Z.; Demir, I.; Uenack, P.; Ichedef, C.; Yurt Kilcar, A. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

2011-07-01

An antitumor agent paclitaxel (PAC) has been proved to be efficient in the treatment of breast and ovarian cancer. Glucuronic acid-derived paclitaxel compound (paclitaxel-glucuronide (PAC-G)) was enzymatically synthesized using microsome preparate separated from rat livers. The biodistribution mechanism of PAC-G in healthy female Albino Wistar rats has been investigated. The expected structure is confirmed according to LC/MS results, and the possible attachment is to C2-hydroxyl group. PAC-G was labeled with {sup 99m}Tc and the radiochemical yield of radiolabeled compound ({sup 99m}Tc-PAC-G) was 98.0 {+-} 02.74% (n=9). The range of the breast/blood and breast/muscle ratios is approximately between 3 and 35 in 240 min. All these experimental studies indicate that {sup 99m}Tc-PAC-G may potentially be used in breast tissue as an imaging agent. (orig.)

NOAA NDBC SOS, 2007-present, currents

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NDBC SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have currents data. Because of the nature of SOS requests, requests for...

NOAA NDBC SOS, 2006-present, winds

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NDBC SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have winds data. Because of the nature of SOS requests, requests for data...

RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer cells.

Science.gov (United States)

Mitsuda, Yoshihide; Morita, Ken; Kashiwazaki, Gengo; Taniguchi, Junichi; Bando, Toshikazu; Obara, Moeka; Hirata, Masahiro; Kataoka, Tatsuki R; Muto, Manabu; Kaneda, Yasufumi; Nakahata, Tatsutoshi; Liu, Pu Paul; Adachi, Souichi; Sugiyama, Hiroshi; Kamikubo, Yasuhiko

2018-04-23

The dual function of runt-related transcriptional factor 1 (RUNX1) as an oncogene or oncosuppressor has been extensively studied in various malignancies, yet its role in gastric cancer remains elusive. Up-regulation of the ErbB2/HER2 signaling pathway is frequently-encountered in gastric cancer and contributes to the maintenance of these cancer cells. This signaling cascade is partly mediated by son of sevenless homolog (SOS) family, which function as adaptor proteins in the RTK cascades. Herein we report that RUNX1 regulates the ErbB2/HER2 signaling pathway in gastric cancer cells through transactivating SOS1 expression, rendering itself an ideal target in anti-tumor strategy toward this cancer. Mechanistically, RUNX1 interacts with the RUNX1 binding DNA sequence located in SOS1 promoter and positively regulates it. Knockdown of RUNX1 led to the decreased expression of SOS1 as well as dephosphorylation of ErbB2/HER2, subsequently suppressed the proliferation of gastric cancer cells. We also found that our novel RUNX inhibitor (Chb-M') consistently led to the deactivation of the ErbB2/HER2 signaling pathway and was effective against several gastric cancer cell lines. Taken together, our work identified a novel interaction of RUNX1 and the ErbB2/HER2 signaling pathway in gastric cancer, which can potentially be exploited in the management of this malignancy.

Influence of Sleeve Gastrectomy on NASH and Type 2 Diabetes Mellitus

Directory of Open Access Journals (Sweden)

W. K. Karcz

2011-01-01

Full Text Available Background. Nonalcoholic fatty liver disease is present in up to 85% of adipose patients and may proceed to nonalcoholic steatohepatitis (NASH. With insulin resistance and obesity being the main risk factors for NASH, the effect of isolated sleeve gastrectomy (ISG on these parameters was examined. Methods. 236 patients underwent ISG with intraoperative liver biopsy from December 2002 to September 2009. Besides demographic data, pre-operative weight/BMI, HbA1c, AST, ALT, triglycerides, HDL and LDL levels were determined. Results. A significant correlation of NASH with higher HbA1c, AST and ALT and lower levels for HDL was observed (P<.05, <.0001, <.0001, <.01, resp.. Overall BMI decreased from 45.0 ± 6.8 to 29.7 ± 6.5 and 31.6 ± 4.4 kg/m2 at 1 and 3 years. An impaired weight loss was demonstrated for patients with NASH and patients with elevated HbA1c (plateau 28.08 kg/m2 versus 29.79 kg/m2 and 32.30 kg/m2 versus 28.79 kg/m2, resp.. Regarding NASH, a significant improvement of AST, ALT, triglyceride and HDL levels was shown (P<.0001 for all. A resolution of elevated HbA1c was observed in 21 of 23 patients. Summary. NASH patients showed a significant loss of body weight and amelioration of NASH status. ISG can be successfully performed in these patients and should be recommended for this subgroup.

The Salt Overly Sensitive (SOS) pathway: established and emerging roles.

Science.gov (United States)

Ji, Hongtao; Pardo, José M; Batelli, Giorgia; Van Oosten, Michael J; Bressan, Ray A; Li, Xia

2013-03-01

Soil salinity is a growing problem around the world with special relevance in farmlands. The ability to sense and respond to environmental stimuli is among the most fundamental processes that enable plants to survive. At the cellular level, the Salt Overly Sensitive (SOS) signaling pathway that comprises SOS3, SOS2, and SOS1 has been proposed to mediate cellular signaling under salt stress, to maintain ion homeostasis. Less well known is how cellularly heterogenous organs couple the salt signals to homeostasis maintenance of different types of cells and to appropriate growth of the entire organ and plant. Recent evidence strongly indicates that different regulatory mechanisms are adopted by roots and shoots in response to salt stress. Several reports have stated that, in roots, the SOS proteins may have novel roles in addition to their functions in sodium homeostasis. SOS3 plays a critical role in plastic development of lateral roots through modulation of auxin gradients and maxima in roots under mild salt conditions. The SOS proteins also play a role in the dynamics of cytoskeleton under stress. These results imply a high complexity of the regulatory networks involved in plant response to salinity. This review focuses on the emerging complexity of the SOS signaling and SOS protein functions, and highlights recent understanding on how the SOS proteins contribute to different responses to salt stress besides ion homeostasis.

Ras activation by SOS

DEFF Research Database (Denmark)

Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen

2014-01-01

Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual ...

Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome–associated Sos1 mutation

Science.gov (United States)

Chen, Peng-Chieh; Wakimoto, Hiroko; Conner, David; Araki, Toshiyuki; Yuan, Tao; Roberts, Amy; Seidman, Christine E.; Bronson, Roderick; Neel, Benjamin G.; Seidman, Jonathan G.; Kucherlapati, Raju

2010-01-01

Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, unique facial features, and congenital heart disease. About 10%–15% of individuals with NS have mutations in son of sevenless 1 (SOS1), which encodes a RAS and RAC guanine nucleotide exchange factor (GEF). To understand the role of SOS1 in the pathogenesis of NS, we generated mice with the NS-associated Sos1E846K gain-of-function mutation. Both heterozygous and homozygous mutant mice showed many NS-associated phenotypes, including growth delay, distinctive facial dysmorphia, hematologic abnormalities, and cardiac defects. We found that the Ras/MAPK pathway as well as Rac and Stat3 were activated in the mutant hearts. These data provide in vivo molecular and cellular evidence that Sos1 is a GEF for Rac under physiological conditions and suggest that Rac and Stat3 activation might contribute to NS phenotypes. Furthermore, prenatal administration of a MEK inhibitor ameliorated the embryonic lethality, cardiac defects, and NS features of the homozygous mutant mice, demonstrating that this signaling pathway might represent a promising therapeutic target for NS. PMID:21041952

The SbSOS1 gene from the extreme halophyte Salicornia brachiata enhances Na+ loading in xylem and confers salt tolerance in transgenic tobacco

Directory of Open Access Journals (Sweden)

Yadav Narendra

2012-10-01

Full Text Available Abstract Background Soil salinity adversely affects plant growth and development and disturbs intracellular ion homeostasis resulting cellular toxicity. The Salt Overly Sensitive 1 (SOS1 gene encodes a plasma membrane Na+/H+ antiporter that plays an important role in imparting salt stress tolerance to plants. Here, we report the cloning and characterisation of the SbSOS1 gene from Salicornia brachiata, an extreme halophyte. Results The SbSOS1 gene is 3774 bp long and encodes a protein of 1159 amino acids. SbSOS1 exhibited a greater level of constitutive expression in roots than in shoots and was further increased by salt stress. Overexpressing the S. brachiata SbSOS1 gene in tobacco conferred high salt tolerance, promoted seed germination and increased root length, shoot length, leaf area, fresh weight, dry weight, relative water content (RWC, chlorophyll, K+/Na+ ratio, membrane stability index, soluble sugar, proline and amino acid content relative to wild type (WT plants. Transgenic plants exhibited reductions in electrolyte leakage, reactive oxygen species (ROS and MDA content in response to salt stress, which probably occurred because of reduced cytosolic Na+ content and oxidative damage. At higher salt stress, transgenic tobacco plants exhibited reduced Na+ content in root and leaf and higher concentrations in stem and xylem sap relative to WT, which suggests a role of SbSOS1 in Na+ loading to xylem from root and leaf tissues. Transgenic lines also showed increased K+ and Ca2+ content in root tissue compared to WT, which reflect that SbSOS1 indirectly affects the other transporters activity. Conclusions Overexpression of SbSOS1 in tobacco conferred a high degree of salt tolerance, enhanced plant growth and altered physiological and biochemical parameters in response to salt stress. In addition to Na+ efflux outside the plasma membrane, SbSOS1 also helps to maintain variable Na+ content in different organs and also affect the other

The SbSOS1 gene from the extreme halophyte Salicornia brachiata enhances Na+ loading in xylem and confers salt tolerance in transgenic tobacco

Science.gov (United States)

2012-01-01

Background Soil salinity adversely affects plant growth and development and disturbs intracellular ion homeostasis resulting cellular toxicity. The Salt Overly Sensitive 1 (SOS1) gene encodes a plasma membrane Na+/H+ antiporter that plays an important role in imparting salt stress tolerance to plants. Here, we report the cloning and characterisation of the SbSOS1 gene from Salicornia brachiata, an extreme halophyte. Results The SbSOS1 gene is 3774 bp long and encodes a protein of 1159 amino acids. SbSOS1 exhibited a greater level of constitutive expression in roots than in shoots and was further increased by salt stress. Overexpressing the S. brachiata SbSOS1 gene in tobacco conferred high salt tolerance, promoted seed germination and increased root length, shoot length, leaf area, fresh weight, dry weight, relative water content (RWC), chlorophyll, K+/Na+ ratio, membrane stability index, soluble sugar, proline and amino acid content relative to wild type (WT) plants. Transgenic plants exhibited reductions in electrolyte leakage, reactive oxygen species (ROS) and MDA content in response to salt stress, which probably occurred because of reduced cytosolic Na+ content and oxidative damage. At higher salt stress, transgenic tobacco plants exhibited reduced Na+ content in root and leaf and higher concentrations in stem and xylem sap relative to WT, which suggests a role of SbSOS1 in Na+ loading to xylem from root and leaf tissues. Transgenic lines also showed increased K+ and Ca2+ content in root tissue compared to WT, which reflect that SbSOS1 indirectly affects the other transporters activity. Conclusions Overexpression of SbSOS1 in tobacco conferred a high degree of salt tolerance, enhanced plant growth and altered physiological and biochemical parameters in response to salt stress. In addition to Na+ efflux outside the plasma membrane, SbSOS1 also helps to maintain variable Na+ content in different organs and also affect the other transporters activity indirectly

A Small-Molecule Inducible Synthetic Circuit for Control of the SOS Gene Network without DNA Damage.

Science.gov (United States)

Kubiak, Jeffrey M; Culyba, Matthew J; Liu, Monica Yun; Mo, Charlie Y; Goulian, Mark; Kohli, Rahul M

2017-11-17

The bacterial SOS stress-response pathway is a pro-mutagenic DNA repair system that mediates bacterial survival and adaptation to genotoxic stressors, including antibiotics and UV light. The SOS pathway is composed of a network of genes under the control of the transcriptional repressor, LexA. Activation of the pathway involves linked but distinct events: an initial DNA damage event leads to activation of RecA, which promotes autoproteolysis of LexA, abrogating its repressor function and leading to induction of the SOS gene network. These linked events can each independently contribute to DNA repair and mutagenesis, making it difficult to separate the contributions of the different events to observed phenotypes. We therefore devised a novel synthetic circuit to unlink these events and permit induction of the SOS gene network in the absence of DNA damage or RecA activation via orthogonal cleavage of LexA. Strains engineered with the synthetic SOS circuit demonstrate small-molecule inducible expression of SOS genes as well as the associated resistance to UV light. Exploiting our ability to activate SOS genes independently of upstream events, we further demonstrate that the majority of SOS-mediated mutagenesis on the chromosome does not readily occur with orthogonal pathway induction alone, but instead requires DNA damage. More generally, our approach provides an exemplar for using synthetic circuit design to separate an environmental stressor from its associated stress-response pathway.

Dendritic Cells Limit Fibro-Inflammatory Injury in NASH

Science.gov (United States)

Henning, Justin R.; Graffeo, Christopher S.; Rehman, Adeel; Fallon, Nina C.; Zambirinis, Constantinos P.; Ochi, Atsuo; Barilla, Rocky; Jamal, Mohsin; Deutsch, Michael; Greco, Stephanie; Ego-Osuala, Melvin; Saeed, Usama Bin; Rao, Raghavendra S.; Badar, Sana; Quesada, Juan P.; Acehan, Devrim; Miller, George

2013-01-01

Non-alcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DC) are antigen presenting cells with an emerging role in hepatic inflammation. We postulated that DC are important in the progression of NASH. We found that intrahepatic DC expand and mature in NASH liver and assume an activated immune-phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibro-inflammation. Our mechanistic studies support a regulatory role for DC in NASH by limiting sterile inflammation via their role in clearance of apoptotic cells and necrotic debris. We found that DC limit CD8+ T cell expansion and restrict Toll-like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Conclusion Our findings support a role for DC in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH. PMID:23322710

Mechanism of SOS-induced targeted and untargeted mutagenesis in E. coli

International Nuclear Information System (INIS)

Maenhaut-Michel, G.

1985-01-01

This paper retraces the evolution of hypotheses concerning mechanisms of SOS induced mutagenesis. Moreover, it reports some recent data which support a new model for the mechanism of targeted and untargeted mutagenesis in E. coli. In summary, the SOS mutator effect, which is responsible for untargeted mutagenesis and perhaps for the misincorporation step in targeted mutagenesis, is believed to involve a fidelity function associated with DNA polymerase III and does not require the umuC gene product. umuC and umuD gene products are probably required specifically for elongation of DNA synthesis past blocking lesions, i.e. to allow mutagenic replication of damaged DNA

Key Inflammatory Processes in Human NASH Are Reflected in Ldlr-/-.Leiden Mice: A Translational Gene Profiling Study.

Science.gov (United States)

Morrison, Martine C; Kleemann, Robert; van Koppen, Arianne; Hanemaaijer, Roeland; Verschuren, Lars

2018-01-01

inflammatory processes (e.g., "Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes," "PI3K signaling in B Lymphocytes") and master regulators (e.g., TNF, CSF2, TGFB1). The majority of these processes and regulators are modulated in the same direction in Ldlr -/- .Leiden mice fed HFD with a human-like macronutrient composition, thus demonstrating that specific experimental conditions recapitulate human disease on the molecular level of disease pathways and upstream/master regulators.

Strong Nash Equilibria and the Potential Maimizer

NARCIS (Netherlands)

van Megen, F.J.C.; Facchini, G.; Borm, P.E.M.; Tijs, S.H.

1996-01-01

A class of non cooperative games characterized by a `congestion e ect' is studied, in which there exists a strong Nash equilibrium, and the set of Nash equilibria, the set of strong Nash equilibria and the set of strategy pro les maximizing the potential function coincide.The structure of the class

Sinusoidal obstruction syndrome (SOS) related to chemotherapy for colorectal liver metastases: factors predictive of severe SOS lesions and protective effect of bevacizumab.

Science.gov (United States)

Hubert, Catherine; Sempoux, Christine; Humblet, Yves; van den Eynde, Marc; Zech, Francis; Leclercq, Isabelle; Gigot, Jean-François

2013-11-01

The most frequent presentation of chemotherapy-related toxicity in colorectal liver metastases (CRLM) is sinusoidal obstruction syndrome (SOS). The purpose of the present study was to identify preoperative factors predictive of SOS and to establish associations between type of chemotherapy and severity of SOS. A retrospective study was carried out in a tertiary academic referral hospital. Patients suffering from CRLM who had undergone resection of at least one liver segment were included. Grading of SOS on the non-tumoral liver parenchyma was accomplished according to the Rubbia-Brandt criteria. A total of 151 patients were enrolled and divided into four groups according to the severity of SOS (grades 0-3). Multivariate analysis identified oxaliplatin and 5-fluorouracil as chemotherapeutic agents responsible for severe SOS lesions (P SOS lesions (P = 0.005). Univariate analysis identified the score on the aspartate aminotransferase : platelets ratio index (APRI) as the most significant biological factor predictive of severe SOS lesions. Splenomegaly is also significantly associated with the occurrence of severe SOS lesions. The APRI score and splenomegaly are effective as factors predictive of SOS. Bevacizumab has a protective effect against SOS. © 2013 International Hepato-Pancreato-Biliary Association.

Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model.

Science.gov (United States)

van Koppen, Arianne; Verschuren, Lars; van den Hoek, Anita M; Verheij, Joanne; Morrison, Martine C; Li, Kelvin; Nagabukuro, Hiroshi; Costessi, Adalberto; Caspers, Martien P M; van den Broek, Tim J; Sagartz, John; Kluft, Cornelis; Beysen, Carine; Emson, Claire; van Gool, Alain J; Goldschmeding, Roel; Stoop, Reinout; Bobeldijk-Pastorova, Ivana; Turner, Scott M; Hanauer, Guido; Hanemaaijer, Roeland

2018-01-01

The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for hepatic fibrosis. A time-course study in low-density lipoprotein-receptor knockout. Leiden mice on a high-fat diet was performed to identify the temporal dynamics of key processes contributing to NASH and fibrosis. An integrative systems biology approach was used to elucidate candidate markers linked to the active fibrosis process by combining transcriptomics, dynamic proteomics, and histopathology. The translational value of these findings were confirmed using human NASH data sets. High-fat-diet feeding resulted in obesity, hyperlipidemia, insulin resistance, and NASH with fibrosis in a time-dependent manner. Temporal dynamics of key molecular processes involved in the development of NASH were identified, including lipid metabolism, inflammation, oxidative stress, and fibrosis. A data-integrative approach enabled identification of the active fibrotic process preceding histopathologic detection using a novel molecular fibrosis signature. Human studies were used to identify overlap of genes and processes and to perform a network biology-based prioritization to rank top candidate markers representing the early manifestation of fibrosis. An early predictive molecular signature was identified that marked the active profibrotic process before histopathologic fibrosis becomes manifest. Early detection of the onset of NASH and fibrosis enables identification of novel blood-based biomarkers to stratify patients at risk, development of new therapeutics, and help shorten (pre)clinical experimental time frames.

76 FR 1664 - Notice of Final Federal Agency Actions on State Highway 99 (Segment G)

Science.gov (United States)

2011-01-11

... on State Highway 99 (Segment G) AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of.... 139(l)(1). The actions relate to a proposed highway project, Grand Parkway (State Highway 99) Segment... (State Highway 99) Segment G from I- 45 to US 59 in Harris and Montgomery Counties; FHWA Project...

Suppression of SOS-inducing activity of chemical mutagens by metabolites from microbial transformation of (-)-isolongifolene.

Science.gov (United States)

Sakata, Kazuki; Oda, Yoshimitsu; Miyazawa, Mitsuo

2010-02-24

In this study, biotransformation of (-)-isolongifolene (1) by Glomerella cingulata and suppressive effect on umuC gene expression by chemical mutagens 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide) and aflatoxin B(1) (AFB(1)) of the SOS response in Salmonella typhimurium TA1535/pSK1002 were investigated. Initially, 1 was carried out the microbial transformation by G. cingulata. The result found that 1 was converted into (-)-isolongifolen-9-one (2), (-)-(2S)-13-hydroxy-isolongifolen-9-one (3), and (-)-(4R)-4-hydroxy-isolongifolen-9-one (4) by G. cingulata, and their conversion rates were 60, 25, and 15%, respectively. The metabolites suppressed the SOS-inducing activity of furylfuramid and AFB(1) in the umu test. Comound 2 showed gene expression by chemical mutagens furylfuramide and AFB(1) was suppressed 54 and 50% at <0.5 mM, respectively. Compound 2 is the most effective compound in this experiment.

Computing Nash equilibria through computational intelligence methods

Science.gov (United States)

Pavlidis, N. G.; Parsopoulos, K. E.; Vrahatis, M. N.

2005-03-01

Nash equilibrium constitutes a central solution concept in game theory. The task of detecting the Nash equilibria of a finite strategic game remains a challenging problem up-to-date. This paper investigates the effectiveness of three computational intelligence techniques, namely, covariance matrix adaptation evolution strategies, particle swarm optimization, as well as, differential evolution, to compute Nash equilibria of finite strategic games, as global minima of a real-valued, nonnegative function. An issue of particular interest is to detect more than one Nash equilibria of a game. The performance of the considered computational intelligence methods on this problem is investigated using multistart and deflection.

NKS/SOS-1 seminar on safety analysis

Energy Technology Data Exchange (ETDEWEB)

Lauridsen, K. [Risoe National Lab., Roskilde (Denmark); Anderson, K. [Karinta-Konsult (Sweden); Pulkkinen, U. [VTT Automation (Finland)

2001-05-01

The report describes presentations and discussions at a seminar held at Risoe on March 22-23, 2000. The title of the seminar was NKS/SOS-1 - Safety Analysis. It dealt with issues of relevance for the safety analysis for the entire nuclear safety field (notably reactors and nuclear waste repositories). Such issues were: objectives of safety analysis, risk criteria, decision analysis, expert judgement and risk communication. In addition, one talk dealt with criteria for chemical industries in Europe. The seminar clearly showed that the concept of risk is multidimensional, which makes clarity and transparency essential elements in risk communication, and that there are issues of common concern between different applications, such as how to deal with different kinds of uncertainty and expert judgement. (au)

NOAA NOS SOS, EXPERIMENTAL - Currents

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have currents data. *These services are for testing and evaluation use...

SOS formats and meta-theory : 20 years after

NARCIS (Netherlands)

Mousavi, M.R.; Reniers, M.A.; Groote, J.F.

2007-01-01

In 1981 Structural Operational Semantics (SOS) was introduced as a systematic way to define operational semantics of programming languages by a set of rules of a certain shape [G.D. Plotkin, A structural approach to operational semantics, Technical Report DAIMI FN-19, Computer Science Department,

Therapy of experimental NASH and fibrosis with galectin inhibitors.

Directory of Open Access Journals (Sweden)

Peter G Traber

Full Text Available Non-alcoholic steatohepatitis (NASH and resultant liver fibrosis is a major health problem without effective therapy. Some data suggest that galectin-3 null mice are resistant to the development of NASH with fibrosis. We examined the ability of two complex carbohydrate drugs that bind galectin-3, GM-CT-01 and GR-MD-02, to treat NASH with fibrosis in a murine model. GR-MD-02 treatment resulted in marked improvement in liver histology with significant reduction in NASH activity and collagen deposition. Treatments seemed also to improve both glomerulopathy and interstitial fibrosis observed in kidneys. The improvement in liver histology was evident when animals were treated early in disease or after establishment of liver fibrosis. In all measures, GM-CT-01 had an intermediate effect between vehicle and GR-MD-02. Galectin-3 protein expression was increased in NASH with highest expression in macrophages surrounding lipid laden hepatocytes, and reduced following treatment with GR-MD-02, while the number of macrophages was unchanged. Treatment with GR-MD-02 also reduced the expression of pathological indicators including iNOS, an important TH1 inflammatory mediator, CD36, a scavenger receptor for lipoproteins on macrophages, and α-smooth muscle actin, a marker for activated stellate cells which are the primary collagen producing cells in liver fibrosis. We conclude that treatment with these galectin-3 targeting drugs improved histopathological findings of NASH and markedly reduced fibrosis in a murine model of NASH. While the mechanisms require further investigation, the treatment effect is associated with a reduction of galectin-3 expressed by activated macrophages which was associated with regression of NASH, including hepatocellular fat accumulation, hepatocyte ballooning, intra-portal and intra-lobular inflammatory infiltrate, and deposition of collagen. Similar effects were found with GM-CT-01, but with approximately four-fold lower potency than

NOAA NOS SOS, EXPERIMENTAL - Wind

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have wind data. *These services are for testing and evaluation use only*...

Coronary artery ectasia in Noonan syndrome: Report of an individual with SOS1 mutation and literature review.

Science.gov (United States)

Calcagni, Giulio; Baban, Anwar; De Luca, Enrica; Leonardi, Benedetta; Pongiglione, Giacomo; Digilio, Maria Cristina

2016-03-01

Noonan syndrome (NS) is the second most frequent hereditary syndrome with cardiac involvement. Pulmonary valve stenosis and hypertrophic cardiomyopathy are the most prevalent cardiovascular abnormalities. We report on a 14-year-old girl with NS due to SOS1 mutation with pulmonary stenosis and idiopathic coronary ectasia. To the best of our knowledge, this is the first report describing coronary ectasia in a patient with NS secondary to a SOS1 mutation. We include a literature review of this rare association. © 2015 Wiley Periodicals, Inc.

Evaluation of 99Tcm nonspecific polyclonal IgG in the detection of rejection in a single lung transplant canine model

International Nuclear Information System (INIS)

Larcos, G.; McLarty, A.J.; McGregor, C.G.A.; Brown, M.L.; Hung, J.C.; O'Connor, M.K.; Tazelaar, H.D.

1993-01-01

Acute rejection is an important cause of graft failure in single lung transplantation, however, current noninvasive tests are neither sensitive nor specific for this diagnosis. The aim of this study was to determine whether 99 Tc m -labelled human nonspecific polyclonal IgG ( 99 Tc m -IgG) may serve as a marker for acute pulmonary rejection following allotransplantation in a dog model. Seventeen mongrel dogs were studied, including four controls and thirteen dogs which underwent surgery [right autotransplant recipient right unmodified allotransplant recipient, and right immunosuppressed allotransplant recipient]. At 6 days following surgery, all dogs received 67 Ga-citrate and 99 Tc m -IgG. Two days later all dogs were sacrified. Post-mortem examination revealed acute lung rejection in nine animals. No significant difference was found in the percentage uptake of both 99 Tc m -IgG and 67 Ga-citrate per gram of tissue between rejecting and nonrejecting transplanted lungs. In cases of moderate to severe rejection, only 67 Ga-citrate showed a significant difference in uptake between rejecting and contralateral native lungs, respectively. We conclude that 99 Tc m -IgG does not accurately identify acute lung rejection in the early postoperative period. (author)

Key Inflammatory Processes in Human NASH Are Reflected in Ldlr−/−.Leiden Mice: A Translational Gene Profiling Study

Science.gov (United States)

Morrison, Martine C.; Kleemann, Robert; van Koppen, Arianne; Hanemaaijer, Roeland; Verschuren, Lars

2018-01-01

inflammatory processes (e.g., “Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes,” “PI3K signaling in B Lymphocytes”) and master regulators (e.g., TNF, CSF2, TGFB1). The majority of these processes and regulators are modulated in the same direction in Ldlr−/−.Leiden mice fed HFD with a human-like macronutrient composition, thus demonstrating that specific experimental conditions recapitulate human disease on the molecular level of disease pathways and upstream/master regulators. PMID:29527177

Local Nash equilibrium in social networks.

Science.gov (United States)

Zhang, Yichao; Aziz-Alaoui, M A; Bertelle, Cyrille; Guan, Jihong

2014-08-29

Nash equilibrium is widely present in various social disputes. As of now, in structured static populations, such as social networks, regular, and random graphs, the discussions on Nash equilibrium are quite limited. In a relatively stable static gaming network, a rational individual has to comprehensively consider all his/her opponents' strategies before they adopt a unified strategy. In this scenario, a new strategy equilibrium emerges in the system. We define this equilibrium as a local Nash equilibrium. In this paper, we present an explicit definition of the local Nash equilibrium for the two-strategy games in structured populations. Based on the definition, we investigate the condition that a system reaches the evolutionary stable state when the individuals play the Prisoner's dilemma and snow-drift game. The local Nash equilibrium provides a way to judge whether a gaming structured population reaches the evolutionary stable state on one hand. On the other hand, it can be used to predict whether cooperators can survive in a system long before the system reaches its evolutionary stable state for the Prisoner's dilemma game. Our work therefore provides a theoretical framework for understanding the evolutionary stable state in the gaming populations with static structures.

Lastekaitsepäeval avati Põltsamaal SOS-peremajad / Raivo Feldmann

Index Scriptorium Estoniae

Feldmann, Raivo

2010-01-01

Eesti teise SOS Lasteküla ametlikul avamisel Põltsamaal 1. juunil 2010. a. osalesid ka Norra suursaadik Eestis Stein Vegard Hagen ja SOS Lasteküla patroon proua Evelin Ilves. Presidendi abikaasa kinkis igale perele pereõunapuu ja koos kirjastusega Varrak igale peremajale väikese koduraamatukogu

Effect of SOS-induced levels of imuABC on spontaneous and damage-induced mutagenesis in Caulobacter crescentus.

Science.gov (United States)

Alves, Ingrid R; Lima-Noronha, Marco A; Silva, Larissa G; Fernández-Silva, Frank S; Freitas, Aline Luiza D; Marques, Marilis V; Galhardo, Rodrigo S

2017-11-01

imuABC (imuAB dnaE2) genes are responsible for SOS-mutagenesis in Caulobacter crescentus and other bacterial species devoid of umuDC. In this work, we have constructed operator-constitutive mutants of the imuABC operon. We used this genetic tool to investigate the effect of SOS-induced levels of these genes upon both spontaneous and damage-induced mutagenesis. We showed that constitutive expression of imuABC does not increase spontaneous or damage-induced mutagenesis, nor increases cellular resistance to DNA-damaging agents. Nevertheless, the presence of the operator-constitutive mutation rescues mutagenesis in a recA background, indicating that imuABC are the only genes required at SOS-induced levels for translesion synthesis (TLS) in C. crescentus. Furthermore, these data also show that TLS mediated by ImuABC does not require RecA, unlike umuDC-dependent mutagenesis in E. coli. Copyright © 2017 Elsevier B.V. All rights reserved.

The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α

Science.gov (United States)

Ren, Tingting; Zhu, Juanjuan; Zhu, Lili; Cheng, Mingliang

2017-01-01

Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets (p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models (p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) (p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway

The meaning of ordered SOS

NARCIS (Netherlands)

Mousavi, M.R.; Phillips, I.C.C.; Reniers, M.A.; Ulidowski, I.; Arun-Kumar, S.; Garg, N.

2006-01-01

Structured Operational Semantics (SOS) is a popular method for defining semantics by means of deduction rules. An important feature of deduction rules, or simply SOS rules, are negative premises, which are crucial in the definitions of such phenomena as priority mechanisms and time-outs. Orderings

A unifying approach to existence of Nash equilibria

NARCIS (Netherlands)

Balder, E.J.

1997-01-01

An approach initiated in [4] is shown to unify results about the existence of (i) Nash equilibria in games with at most countably many players, (ii) Cournot-Nash equilibrium distributions for large, anonymous games, and (iii) Nash equilibria (both mixed and pure) for continuum games. A new, central

The SOS response increases bacterial fitness, but not evolvability, under a sublethal dose of antibiotic.

Science.gov (United States)

Torres-Barceló, Clara; Kojadinovic, Mila; Moxon, Richard; MacLean, R Craig

2015-10-07

Exposure to antibiotics induces the expression of mutagenic bacterial stress-response pathways, but the evolutionary benefits of these responses remain unclear. One possibility is that stress-response pathways provide a short-term advantage by protecting bacteria against the toxic effects of antibiotics. Second, it is possible that stress-induced mutagenesis provides a long-term advantage by accelerating the evolution of resistance. Here, we directly measure the contribution of the Pseudomonas aeruginosa SOS pathway to bacterial fitness and evolvability in the presence of sublethal doses of ciprofloxacin. Using short-term competition experiments, we demonstrate that the SOS pathway increases competitive fitness in the presence of ciprofloxacin. Continued exposure to ciprofloxacin results in the rapid evolution of increased fitness and antibiotic resistance, but we find no evidence that SOS-induced mutagenesis accelerates the rate of adaptation to ciprofloxacin during a 200 generation selection experiment. Intriguingly, we find that the expression of the SOS pathway decreases during adaptation to ciprofloxacin, and this helps to explain why this pathway does not increase long-term evolvability. Furthermore, we argue that the SOS pathway fails to accelerate adaptation to ciprofloxacin because the modest increase in the mutation rate associated with SOS mutagenesis is offset by a decrease in the effective strength of selection for increased resistance at a population level. Our findings suggest that the primary evolutionary benefit of the SOS response is to increase bacterial competitive ability, and that stress-induced mutagenesis is an unwanted side effect, and not a selected attribute, of this pathway. © 2015 The Authors.

Comparison of biological behavior of 99Tcm-ciprofloxacin (Infecton) and 99Tcm-HIgG in rabbit models of inflammation

International Nuclear Information System (INIS)

He Wei; Chen Shaoliang; Mao Jinlei; Jiang Maosong

2008-01-01

Objective: 99 Tc m -ciprofloxacin(Infecton) and 99 Tc m -HIgG are both radiopharmaceuticals for inflammation and infectious disease imaging. It was reported that 99 Tc m -ciprofloxacin (Infecton)was able to distinguish inflammation from infection, while 99 Tc m -HIgG was a nonspecific agent. The study was designed to compare the in vivo characteristics between 99 Tc m -ciprofloxacin(Infecton) and 99 Tc m -HIgC in rabbit model of inflammation. Methods: Eight rabbits were grouped as inflammation model (the first group), infection mod- el (the second group), concomitant inflammation and infection model (the third group), and control (the fourth group) groups. A total of 185 MBq (0.5 ml) 99 Tc m -ciprofloxacin (Infecton) was administered intravenously to each rabbit, a serious dynamic images were acquired till 24 h post-injection. Repeated examination with 99 Tc m -HIgG was carried out 2 d later. Results: 99 Tc m -ciprofloxacin (Infecton) scan was negative in the inflammation models and controls, and was positive in the infection models. In the third group 99 Tc m - ciprofloxacin (Infecton) showed infection focus in the left thigh but negative uptake at inflammation focus in the right thigh. 99 Tc m -HIgG scan were positive in all models. The optimal image time for 99 Tc m -ciproftoxacin (Infecton) was 3 h after administration, but positive image could still be observed 24 h later. Conclusion 99 Tc m -ciprofloxacin (Infecton) appears to specifically accumulate in the infective lesion. (authors)

Evaluation of effects of busulfan and DMA on SOS in pediatric stem cell recipients.

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Kerl, Kornelius; Diestelhorst, Christian; Bartelink, Imke; Boelens, Jaap; Trame, Mirjam N; Boos, Joachim; Hempel, Georg

2014-02-01

Busulfan (Bu) is a DNA-alkylating agent used for myeloablative conditioning in stem cell transplantation in children and adults. While the use of intravenous rather than oral administration of Bu has reduced inter-individual variability in plasma levels, toxicity still occurs frequently after hematopoietic stem cell transplantation (HSCT). Toxicity (especially hepatotoxic effects) of intravenous (IV) Bu may be related to both Bu and/or N,N-dimethylacetamide (DMA), the solvent of Bu. In this study, we assessed the relation between the exposure of Bu and DMA with regards to the clinical outcome in children from two cohorts. In a two-centre study Bu and DMA AUC (area under the curve) were correlated in pediatric stem cell recipients to the risk of developing SOS and to the clinical outcome. In patients receiving Bu four times per day Bu levels >1,500 µmol/L minute correlate to an increased risk of developing a SOS. In the collective cohort, summarizing data of all 53 patients of this study, neither high area under the curve (AUC) of Bu nor high AUC of DMA appears to be an independent risk factor for the development of SOS in children. In this study neither Bu nor DMA was observed as an independent risk factor for the development of SOS. To identify subgroups (e.g., infants), in which Bu or DMA might be risk factors for the induction of SOS, larger cohorts have to be evaluated. © 2013 Wiley Periodicals, Inc.

NOAA NDBC SOS, 2006-present, sea_water_temperature

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NDBC SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have sea_water_temperature data. Because of the nature of SOS requests,...

SNAP Operating System (SOS) user's guide

International Nuclear Information System (INIS)

Sabuda, J.D.; Polito, J.; Walker, J.L.; Grant, F.H. III.

1982-03-01

The SNAP Operating System (SOS) is a FORTRAN 77 program which provides assistance to the safeguards analyst who uses the Safeguards Automated Facility Evaluation (SAFE) and the Safeguards Network Analysis Procedure (SNAP) techniques. Features offered by SOS are a data base system for storing a library of SNAP applications, computer graphics representation of SNAP models, a computer graphics editor to develop and modify SNAP models, a SAFE-to-SNAP interface, automatic generation of SNAP input data, and a computer graphics postprocessor for SNAP. The SOS User's Guide is designed to provide the user with the information necessary to use SOS effectively. Examples are used throughout to illustrate the concepts. The format of the user's guide follows the same sequence as would be used in executing an actual application

99mTc complexes of 1,3-propanedithiol derivatives

International Nuclear Information System (INIS)

Alagui, A.; Apparu, M.; Vidal, M.; Mathieu, J.P.

1987-01-01

The labelling of 1,3-n alkylpropanedithiols and of 15-(1,3-dimercapto 2-propyl)pentadecanoic acid by 99m Tc was performed by an exchange reaction with the hexachlorotechnetate ion 99m TcCl 6 2- and by reduction of 99m TcO 4 - with Sn(II) in the presence of the ligand. The biological distribution of the exotechnetium complexes obtained by the latter method in mouse does not reveal a high tropism of these labelling compounds in relation to a particular tissue. (author) 14 refs.; 2 tabs

Proteomic and lipidomic signatures of lipid metabolism in NASH-associated hepatocellular carcinoma.

Science.gov (United States)

Muir, Kyle; Hazim, Antonious; He, Ying; Peyressatre, Marion; Kim, Do-Young; Song, Xiaoling; Beretta, Laura

2013-08-01

Nonalcoholic steatohepatitis (NASH) is a common preneoplastic condition of hepatocellular carcinoma (HCC). Mice with hepatocytic deletion of Pten develop NASH and HCC later in life. This model is highly valuable for studies aimed at identifying the molecular mechanism by which metabolic disorders contribute to tumor development. We applied proteomic and lipidomic profiling approaches to Pten-null NASH liver and tumors. Circulating fatty acid composition was also characterized in these mice. The relevance to human NASH and HCC was further validated. This integrative proteomic and lipidomic study from mouse to human and from liver to blood identified the following disease signatures: (i) an HCC signature: upregulated hepatic scd1/scd2, fads2, and acsl5:acsl1 ratio, elevated vaccenic and erucic acids, and reduced margaric and linoleic acids in both liver and plasma; (ii) a NASH signature that correlates with tumor burden: upregulated hepatic elovl6, elevated oleic, adrenic, and osbond acids, and reduced cervonic acid in liver and plasma; and (iii) a NASH signature: reduced hepatic and circulating lignoceric and eicosapentaenoic acids. Altogether, these results show the role of lipid-modifying enzymes converting saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA) in HCC and the importance of an increased ratio of long chain n6-polyunsaturated fatty acids over n3-polyunsaturated fatty acids in NASH and HCC risk. They also highlight the relevance of the Pten-null model for studies related to NASH and HCC and show that circulating lipid metabolome provides a direct read of lipid changes in the liver. Most importantly, novel candidate targets for HCC diagnosis, therapy, risk assessment, and prevention were identified. ©2013 AACR.

Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model

NARCIS (Netherlands)

Koppen, A. van; Verschuren, L.; Hoek, A.M. van den; Verheij, J.; Morrison, M.C.; Li, K.; Nagabukuro, H.; Costessi, A.; Caspers, M.P.M.; Broek, T.J. van den; Sagartz, J.; Kluft, C.; Beysen, C.; Emson, C.; Gool, A.J. van; Goldschmeding, R.; Stoop, R.; Bobeldijk-Pastorova, I.; Turner, S.M.; Hanauer, G.; Hanemaaijer, R.

2017-01-01

Background & Aims: The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes

One-way membrane trafficking of SOS in receptor-triggered Ras activation.

Science.gov (United States)

Christensen, Sune M; Tu, Hsiung-Lin; Jun, Jesse E; Alvarez, Steven; Triplet, Meredith G; Iwig, Jeffrey S; Yadav, Kamlesh K; Bar-Sagi, Dafna; Roose, Jeroen P; Groves, Jay T

2016-09-01

SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2-SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide linkage to the membrane. In reconstituted-membrane experiments, these Grb2-independent interactions were sufficient to retain human SOS on the membrane for many minutes, during which a single SOS molecule could processively activate thousands of Ras molecules. These observations raised questions concerning how receptors maintain control of SOS in cells and how membrane-recruited SOS is ultimately released. We addressed these questions in quantitative assays of reconstituted SOS-deficient chicken B-cell signaling systems combined with single-molecule measurements in supported membranes. These studies revealed an essentially one-way trafficking process in which membrane-recruited SOS remains trapped on the membrane and continuously activates Ras until being actively removed via endocytosis.

The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1.

Science.gov (United States)

Rozakis-Adcock, M; Fernley, R; Wade, J; Pawson, T; Bowtell, D

1993-05-06

Many tyrosine kinases, including the receptors for hormones such as epidermal growth factor (EGF), nerve growth factor and insulin, transmit intracellular signals through Ras proteins. Ligand binding to such receptors stimulates Ras guanine-nucleotide-exchange activity and increases the level of GTP-bound Ras, suggesting that these tyrosine kinases may activate a guanine-nucleotide releasing protein (GNRP). In Caenorhabditis elegans and Drosophila, genetic studies have shown that Ras activation by tyrosine kinases requires the protein Sem-5/drk, which contains a single Src-homology (SH) 2 domain and two flanking SH3 domains. Sem-5 is homologous to the mammalian protein Grb2, which binds the autophosphorylated EGF receptor and other phosphotyrosine-containing proteins such as Shc through its SH2 domain. Here we show that in rodent fibroblasts, the SH3 domains of Grb2 are bound to the proline-rich carboxy-terminal tail of mSos1, a protein homologous to Drosophila Sos. Sos is required for Ras signalling and contains a central domain related to known Ras-GNRPs. EGF stimulation induces binding of the Grb2-mSos1 complex to the autophosphorylated EGF receptor, and mSos1 phosphorylation. Grb2 therefore appears to link tyrosine kinases to a Ras-GNRP in mammalian cells.

Tolerance of Escherichia coli to fluoroquinolone antibiotics depends on specific components of the SOS response pathway.

Science.gov (United States)

Theodore, Alyssa; Lewis, Kim; Vulic, Marin

2013-12-01

Bacteria exposed to bactericidal fluoroquinolone (FQ) antibiotics can survive without becoming genetically resistant. Survival of these phenotypically resistant cells, commonly called "persisters," depends on the SOS gene network. We have examined mutants in all known SOS-regulated genes to identify functions essential for tolerance in Escherichia coli. The absence of DinG and UvrD helicases and the Holliday junction processing enzymes RuvA and RuvB leads to a decrease in survival. Analysis of the respective mutants indicates that, in addition to repair of double-strand breaks, tolerance depends on the repair of collapsed replication forks and stalled transcription complexes. Mutation in recF results in increased survival, which identifies RecAF recombination as a poisoning mechanism not previously linked to FQ lethality. DinG acts upstream of SOS promoting its induction, whereas RuvAB participates in repair only. UvrD directly promotes all repair processes initiated by FQ-induced damage and prevents RecAF-dependent misrepair, making it one of the crucial SOS functions required for tolerance.

SOS response activation and competence development are antagonistic mechanisms in Streptococcus thermophilus.

Science.gov (United States)

Boutry, Céline; Delplace, Brigitte; Clippe, André; Fontaine, Laetitia; Hols, Pascal

2013-02-01

Streptococcus includes species that either contain or lack the LexA-like repressor (HdiR) of the classical SOS response. In Streptococcus pneumoniae, a species which belongs to the latter group, SOS response inducers (e.g., mitomycin C [Mc] and fluoroquinolones) were shown to induce natural transformation, leading to the hypothesis that DNA damage-induced competence could contribute to genomic plasticity and stress resistance. Using reporter strains and microarray experiments, we investigated the impact of the SOS response inducers mitomycin C and norfloxacin and the role of HdiR on competence development in Streptococcus thermophilus. We show that both the addition of SOS response inducers and HdiR inactivation have a dual effect, i.e., induction of the expression of SOS genes and reduction of transformability. Reduction of transformability results from two different mechanisms, since HdiR inactivation has no major effect on the expression of competence (com) genes, while mitomycin C downregulates the expression of early and late com genes in a dose-dependent manner. The downregulation of com genes by mitomycin C was shown to take place at the level of the activation of the ComRS signaling system by an unknown mechanism. Conversely, we show that a ComX-deficient strain is more resistant to mitomycin C and norfloxacin in a viability plate assay, which indicates that competence development negatively affects the resistance of S. thermophilus to DNA-damaging agents. Altogether, our results strongly suggest that SOS response activation and competence development are antagonistic processes in S. thermophilus.

Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor.

Science.gov (United States)

McDonald, Caleb B; Bhat, Vikas; Kurouski, Dmitry; Mikles, David C; Deegan, Brian J; Seldeen, Kenneth L; Lednev, Igor K; Farooq, Amjad

2013-01-01

Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like conformation in solution. Of particular interest is the observation that while chemical denaturation of PR domain results in the formation of a significant amount of polyproline II (PPII) helices, it has little or negligible effect on its overall size as measured by its hydrodynamic radius. Our data also show that the PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations. Collectively, our study provides new insights into the conformational equilibrium of a key signaling molecule with important consequences on its physiological function. Copyright © 2013 Elsevier B.V. All rights reserved.

An orthosteric inhibitor of the RAS-SOS interaction.

Science.gov (United States)

Nickerson, Seth; Joy, Stephen T; Arora, Paramjit S; Bar-Sagi, Dafna

2013-01-01

Rat sarcoma (RAS) proteins are signaling nodes that transduce extracellular cues into precise alterations in cellular physiology by engaging effector pathways. RAS signaling thus regulates diverse cell processes including proliferation, migration, differentiation, and survival. Owing to this central role in governing mitogenic signals, RAS pathway components are often dysregulated in human diseases. Targeted therapy of RAS pathways has generally not been successful, largely because of the robust biochemistry of the targets and their multifaceted network of molecular regulators. The rate-limiting step of RAS activation is Son of Sevenless (SOS)-mediated nucleotide exchange involving a single evolutionarily conserved catalytic helix from SOS. Structure function data of this mechanism provided a strong platform to design an SOS-derived, helically constrained peptide mimic as an inhibitor of the RAS-SOS interaction. In this chapter, we review RAS-SOS signaling dynamics and present evidence supporting the novel paradigm of inhibiting their interaction as a therapeutic strategy. We then describe a method of generating helically constrained peptide mimics of protein surfaces, which we have employed to inhibit the RAS-SOS active site interaction. The biochemical and functional properties of this SOS mimic support the premise that inhibition of RAS-nucleotide exchange can effectively block RAS activation and downstream signaling. © 2013 Elsevier Inc. All rights reserved.

SOS1 gene polymorphisms are associated with gestational diabetes mellitus in a Chinese population: Results from a nested case-control study in Taiyuan, China.

Science.gov (United States)

Chen, Qiong; Yang, Hailan; Feng, Yongliang; Zhang, Ping; Wu, Weiwei; Li, Shuzhen; Thompson, Brian; Wang, Xin; Peng, Tingting; Wang, Fang; Xie, Bingjie; Guo, Pengge; Li, Mei; Wang, Ying; Zhao, Nan; Wang, Suping; Zhang, Yawei

2018-03-01

Gestational diabetes mellitus is a growing public health concern due to its large disease burden; however, the underlying pathophysiology remains unclear. Therefore, we examined the relationship between 107 single-nucleotide polymorphisms in insulin signalling pathway genes and gestational diabetes mellitus risk using a nested case-control study. The SOS1 rs7598922 GA and AA genotype were statistically significantly associated with reduced gestational diabetes mellitus risk ( p trend  = 0.0006) compared with GG genotype. At the gene level, SOS1 was statistically significantly associated with gestational diabetes mellitus risk after adjusting for multiple comparisons. Moreover, AGGA and GGGG haplotypes in SOS1 gene were associated with reduced risk of gestational diabetes mellitus. Our study provides evidence for an association between the SOS1 gene and risk of gestational diabetes mellitus; however, its role in the pathogenesis of gestational diabetes mellitus will need to be verified by further studies.

Semantics and expressiveness of ordered SOS

NARCIS (Netherlands)

Mousavi, M.R.; Phillips, I.C.C.; Reniers, M.A.; Ulidowski, I.

2009-01-01

Structured Operational Semantics (SOS) is a popular method for defining semantics by means of transition rules. An important feature of SOS rules is negative premises, which are crucial in the definitions of such phenomena as priority mechanisms and time-outs. However, the inclusion of negative

Obeticholic acid raises LDL-cholesterol and reduces HDL-cholesterol in the Diet-Induced NASH (DIN) hamster model.

Science.gov (United States)

Briand, François; Brousseau, Emmanuel; Quinsat, Marjolaine; Burcelin, Rémy; Sulpice, Thierry

2018-01-05

The use of rat and mouse models limits the translation to humans for developing novel drugs targeting nonalcoholic steatohepatitis (NASH). Obeticholic acid (OCA) illustrates this limitation since its dyslipidemic effect in humans cannot be observed in these rodents. Conversely, Golden Syrian hamsters have a lipoprotein metabolism mimicking human dyslipidemia since it does express the cholesteryl ester transfer protein (CETP). We therefore developed a Diet-Induced NASH (DIN) hamster model and evaluated the impact of OCA. Compared with chow fed controls, hamsters fed for 20 weeks with a free-choice (FC) diet, developed obesity, insulin resistance, dyslipidemia and NASH (microvesicular steatosis, inflammation, hepatocyte ballooning and perisinusoidal to bridging fibrosis). After 20 weeks of diet, FC fed hamsters were treated without or with obeticholic acid (15mg/kg/day) for 5 weeks. Although a non-significant trend towards higher dietary caloric intake was observed, OCA significantly lowered body weight after 5 weeks of treatment. OCA significantly increased CETP activity and LDL-C levels by 20% and 27%, and reduced HDL-C levels by 20%. OCA blunted hepatic gene expression of Cyp7a1 and Cyp8b1 and reduced fecal bile acids mass excretion by 64% (P OCA showed a trend towards higher scavenger receptor Class B type I (SR-BI) and lower LDL-receptor hepatic protein expression. OCA reduced NAS score for inflammation (P OCA as observed in humans, and should be useful for evaluating novel drugs targeting NASH. Copyright © 2017 Elsevier B.V. All rights reserved.

Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model

Energy Technology Data Exchange (ETDEWEB)

Stefano, J.T.; Pereira, I.V.A.; Torres, M.M.; Bida, P.M. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Coelho, A.M.M. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Xerfan, M.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Cogliati, B. [Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Barbeiro, D.F. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mazo, D.F.C. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Kubrusly, M.S.; D' Albuquerque, L.A.C. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Souza, H.P. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carrilho, F.J.; Oliveira, C.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

2015-02-24

Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg{sup -1}·day{sup -1} by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.

Ribonuclease E modulation of the bacterial SOS response.

Directory of Open Access Journals (Sweden)

Robert Manasherob

Full Text Available Plants, animals, bacteria, and Archaea all have evolved mechanisms to cope with environmental or cellular stress. Bacterial cells respond to the stress of DNA damage by activation of the SOS response, the canonical RecA/LexA-dependent signal transduction pathway that transcriptionally derepresses a multiplicity of genes-leading to transient arrest of cell division and initiation of DNA repair. Here we report the previously unsuspected role of E. coli endoribonuclease RNase E in regulation of the SOS response. We show that RNase E deletion or inactivation of temperature-sensitive RNase E protein precludes normal initiation of SOS. The ability of RNase E to regulate SOS is dynamic, as down regulation of RNase E following DNA damage by mitomycin C resulted in SOS termination and restoration of RNase E function leads to resumption of a previously aborted response. Overexpression of the RraA protein, which binds to the C-terminal region of RNase E and modulates the actions of degradosomes, recapitulated the effects of RNase E deficiency. Possible mechanisms for RNase E effects on SOS are discussed.

Ribonuclease E modulation of the bacterial SOS response.

Science.gov (United States)

Manasherob, Robert; Miller, Christine; Kim, Kwang-sun; Cohen, Stanley N

2012-01-01

Plants, animals, bacteria, and Archaea all have evolved mechanisms to cope with environmental or cellular stress. Bacterial cells respond to the stress of DNA damage by activation of the SOS response, the canonical RecA/LexA-dependent signal transduction pathway that transcriptionally derepresses a multiplicity of genes-leading to transient arrest of cell division and initiation of DNA repair. Here we report the previously unsuspected role of E. coli endoribonuclease RNase E in regulation of the SOS response. We show that RNase E deletion or inactivation of temperature-sensitive RNase E protein precludes normal initiation of SOS. The ability of RNase E to regulate SOS is dynamic, as down regulation of RNase E following DNA damage by mitomycin C resulted in SOS termination and restoration of RNase E function leads to resumption of a previously aborted response. Overexpression of the RraA protein, which binds to the C-terminal region of RNase E and modulates the actions of degradosomes, recapitulated the effects of RNase E deficiency. Possible mechanisms for RNase E effects on SOS are discussed.

Collection for SOS animaux

CERN Multimedia

2005-01-01

The Pays de Gex animal shelter is collecting funds. There will be things to buy. You will be able to make a donation and/or become a member of the association or simply get information. SOS Animaux stall (Hall, Build. 60, next to restaurant 1) On Wednesday 23 November 2005 (from 9h - 17h non-stop)

Nash social welfare in multiagent resource allocation

NARCIS (Netherlands)

Ramezani, S.; Endriss, U.; David, E.; Gerding, E.; Sarne, D.; Shehory, O.

2010-01-01

We study different aspects of the multiagent resource allocation problem when the objective is to find an allocation that maximizes Nash social welfare, the product of the utilities of the individual agents. The Nash solution is an important welfare criterion that combines efficiency and fairness

NOAA NDBC SOS, 2007-present, sea_water_practical_salinity

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NDBC SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have sea_water_practical_salinity data. Because of the nature of SOS...

Structural analyses of polymorphic transitions of sn-1, 3-distearoyl-2-oleoylglycerol (SOS) and sn-1, 3-dioleoyl-2-stearoylglycerol (OSO): assessment on steric hindrance of unsaturated and saturated acyl chain interactions.

Science.gov (United States)

Yano, J; Sato, K; Kaneko, F; Small, D M; Kodali, D R

1999-01-01

Polymorphic transformations in two saturated-unsaturated mixed acid triacylglycerols, SOS (sn -1,3-distearoyl-2-oleoylglycerol) and OSO (sn -1,3-dioleoyl-2-stearoylglycerol), have been studied by FT-IR spectroscopy using deuterated specimens in which stearoyl chains are fully deuterated. A reversible phase transition between sub alpha and alpha and a series of irreversible transitions (alpha-->gamma-->beta'-->beta (beta2, beta1) for SOS and alpha-->beta'-->beta for OSO) were studied with an emphasis on the conformational ordering process of stearoyl and oleoyl chains. The alpha-->sub alpha reversible transition was due to the orientational change of stearoyl chains in the lateral directions from the hexagonal subcell to a perpendicularly packed one. As the first stage of the series of irreversible transitions from alpha to beta, the conformational ordering of saturated chains took place in the alpha-->gamma transition of SOS and in the alpha-->beta' transition of OSO; one stearoyl chain in SOS and OSO takes the all-trans conformation and the second stearoyl chain in SOS takes the bent conformation like those observed in the most stable beta-type. As the final stage, the ordering of unsaturated chains occurred in the beta'-->beta transition both for SOS and OSO. A conversion in the layered structure from bilayer to trilayer was also accompanied by the conformational ordering in the alpha-->gamma transition of SOS and in the beta'-->beta transition of OSO.

Nash equilibria via duality and homological selection

Indian Academy of Sciences (India)

1Quantitative Methods and Information Systems Area, Indian Institute ... The original proof of existence of Nash equilibria [13] uses fairly ...... The fiber over a regular point a of the disk Di consists of three inverse images (labeled. A1,A2,A3 in ...

Enhanced A-FABP expression in visceral fat: potential contributor to the progression of NASH

Directory of Open Access Journals (Sweden)

Min Yong Yoon

2012-09-01

Full Text Available Background/AimsAdipose tissue is an active endocrine organ that secretes various metabolically important substances including adipokines, which represent a link between insulin resistance and nonalcoholic steatohepatitis (NASH. The factors responsible for the progression from simple steatosis to steatohepatitis remain elusive, but adipokine imbalance may play a pivotal role. We evaluated the expressions of adipokines such as visfatin, adipocyte-fatty-acid-binding protein (A-FABP, and retinol-binding protein-4 (RBP-4 in serum and tissue. The aim was to discover whether these adipokines are potential predictors of NASH.MethodsPolymerase chain reaction, quantification of mRNA, and Western blots encoding A-FABP, RBP-4, and visfatin were used to study tissue samples from the liver, and visceral and subcutaneous adipose tissue. The tissue samples were from biopsy specimens obtained from patients with proven NASH who were undergoing laparoscopic cholecystectomy due to gallbladder polyps.ResultsPatients were classified into two groups: NASH, n=10 and non-NASH, n=20 according to their nonalcoholic fatty liver disease Activity Score. Although serum A-FABP levels did not differ between the two groups, the expressions of A-FABP mRNA and protein in the visceral adipose tissue were significantly higher in NASH group than in non-NASH group (104.34 vs. 97.05, P<0.05, and 190.01 vs. 95.15, P<0.01, respectively. Furthermore, the A-FABP protein expression ratio between visceral adipose tissue and liver was higher in NASH group than in non-NASH group (4.38 vs. 1.64, P<0.05.ConclusionsNASH patients had higher levels of A-FABP expression in their visceral fat compared to non-NASH patients. This differential A-FABP expression may predispose patients to the progressive form of NASH.

Nominal SOS

NARCIS (Netherlands)

Cimini, M.; Mousavi, M.R.; Reniers, M.A.; Gabbay, M.J.

2012-01-01

Plotkin's style of Structural Operational Semantics (SOS) has become a de facto standard in giving operational semantics to formalisms and process calculi. In many such formalisms and calculi, the concepts of names, variables and binders are essential ingredients. In this paper, we propose a formal

Inhibitors of Ras-SOS Interactions.

Science.gov (United States)

Lu, Shaoyong; Jang, Hyunbum; Zhang, Jian; Nussinov, Ruth

2016-04-19

Activating Ras mutations are found in about 30 % of human cancers. Ras activation is regulated by guanine nucleotide exchange factors, such as the son of sevenless (SOS), which form protein-protein interactions (PPIs) with Ras and catalyze the exchange of GDP by GTP. This is the rate-limiting step in Ras activation. However, Ras surfaces lack any evident suitable pockets where a molecule might bind tightly, rendering Ras proteins still 'undruggable' for over 30 years. Among the alternative approaches is the design of inhibitors that target the Ras-SOS PPI interface, a strategy that is gaining increasing recognition for treating Ras mutant cancers. Herein we focus on data that has accumulated over the past few years pertaining to the design of small-molecule modulators or peptide mimetics aimed at the interface of the Ras-SOS PPI. We emphasize, however, that even if such Ras-SOS therapeutics are potent, drug resistance may emerge. To counteract this development, we propose "pathway drug cocktails", that is, drug combinations aimed at parallel (or compensatory) pathways. A repertoire of classified cancer, cell/tissue, and pathway/protein combinations would be beneficial toward this goal. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: association of pancreatic exocrine deficiency and infection.

Science.gov (United States)

Murata, Yasuhiro; Mizuno, Shugo; Kato, Hiroyuki; Kishiwada, Masashi; Ohsawa, Ichiro; Hamada, Takashi; Usui, Masanobu; Sakurai, Hiroyuki; Tabata, Masami; Nishimura, Keisuke; Fukutome, Kazuo; Isaji, Shuji

2011-08-01

Previous clinical study has demonstrated that 30-40% of patients undergoing pancreaticoduodenectomy (PD) developed hepatic steatosis. However, nonalcoholic steatohepatitis (NASH) is a little-known complication after PD. Recently we encountered two patients with PD who later developed NASH diagnosed by liver biopsy. Case 1 was a 79-year-old woman who underwent PD for intraductal papillary mucinous neoplasm (IPMN). She had postoperative severe diarrhea due to pseudomembranous enterocolitis. Severe liver dysfunction was observed on the 31st postoperative day. Abdominal computed tomography (CT) on the 32nd day showed remarkably decreased hepatic CT value of 6 HU. Immediate liver biopsy revealed NASH (Brunt criteria: grade 2, stage 2). Case 2 was a 71-year-old woman who underwent PD for IPMN. Liver biopsy on 70th postoperative day, which was performed for assessment of moderate liver dysfunction and decreased hepatic CT value of 44 HU, demonstrated simple steatosis. In the 21st postoperative month, she developed severe urinary tract infection together with marked liver dysfunction. Immediate liver biopsy revealed NASH (Brunt criteria: grade 1, stage 1). For each patient, treatment of infection and high-dose pancreatic enzyme supplements improved liver dysfunction and liver steatosis. Clinical features of our cases seem to support the current leading hypothesis of the pathogenesis of NASH, i.e., the two-hit theory.

NOAA NOS SOS, EXPERIMENTAL, 1902-present, Salinity

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have salinity data. *These services are for testing and evaluation use...

NOAA NOS SOS, EXPERIMENTAL, 1902-present, Conductivity

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have conductivity data. *These services are for testing and evaluation use...

Blocking by the carcinogen, L-ethionine, of SOS functions in a tif-1 mutant of Escherichia coli B/r

International Nuclear Information System (INIS)

Wiesner, R.; Troll, W.

1981-01-01

In Escherichia coli, DNA damage by carcinogenic agents results in the coordinate expression of a diversity of functions (SOS functions), many of which are thermally inducible without any damage to DNA in a tif-1 mutant. These include prophage induction, filamentous growth, and an error-prone DNA repair activity, which is responsible for ultraviolet-induced mutagenesis. Ethionine causes hepatic carcinoma in rats after prolonged feeding but is not a mutagen in the Ames test. The present study shows that 10 mM ethionine prevents the thermal induction of lambda-prophage in a tif-1 derivative of E. coli. The enhancement of mutation, which normally occurs at high temperature after a low dose of ultraviolet light, is also blocked by ethionine. Ethionine does not block, to any appreciable extent, the incorporation of radioactive precursors into RNA, DNA, or protein

DinB Upregulation Is the Sole Role of the SOS Response in Stress-Induced Mutagenesis in Escherichia coli

Science.gov (United States)

Galhardo, Rodrigo S.; Do, Robert; Yamada, Masami; Friedberg, Errol C.; Hastings, P. J.; Nohmi, Takehiko; Rosenberg, Susan M.

2009-01-01

Stress-induced mutagenesis is a collection of mechanisms observed in bacterial, yeast, and human cells in which adverse conditions provoke mutagenesis, often under the control of stress responses. Control of mutagenesis by stress responses may accelerate evolution specifically when cells are maladapted to their environments, i.e., are stressed. It is therefore important to understand how stress responses increase mutagenesis. In the Escherichia coli Lac assay, stress-induced point mutagenesis requires induction of at least two stress responses: the RpoS-controlled general/starvation stress response and the SOS DNA-damage response, both of which upregulate DinB error-prone DNA polymerase, among other genes required for Lac mutagenesis. We show that upregulation of DinB is the only aspect of the SOS response needed for stress-induced mutagenesis. We constructed two dinB(oc) (operator-constitutive) mutants. Both produce SOS-induced levels of DinB constitutively. We find that both dinB(oc) alleles fully suppress the phenotype of constitutively SOS-“off” lexA(Ind−) mutant cells, restoring normal levels of stress-induced mutagenesis. Thus, dinB is the only SOS gene required at induced levels for stress-induced point mutagenesis. Furthermore, although spontaneous SOS induction has been observed to occur in only a small fraction of cells, upregulation of dinB by the dinB(oc) alleles in all cells does not promote a further increase in mutagenesis, implying that SOS induction of DinB, although necessary, is insufficient to differentiate cells into a hypermutable condition. PMID:19270270

Factors limiting SOS expression in log-phase cells of Escherichia coli.

Science.gov (United States)

Massoni, Shawn C; Leeson, Michael C; Long, Jarukit Edward; Gemme, Kristin; Mui, Alice; Sandler, Steven J

2012-10-01

In Escherichia coli, RecA-single-stranded DNA (RecA-ssDNA) filaments catalyze DNA repair, recombination, and induction of the SOS response. It has been shown that, while many (15 to 25%) log-phase cells have RecA filaments, few (about 1%) are induced for SOS. It is hypothesized that RecA's ability to induce SOS expression in log-phase cells is repressed because of the potentially detrimental effects of SOS mutagenesis. To test this, mutations were sought to produce a population where the number of cells with SOS expression more closely equaled the number of RecA filaments. Here, it is shown that deleting radA (important for resolution of recombination structures) and increasing recA transcription 2- to 3-fold with a recAo1403 operator mutation act independently to minimally satisfy this condition. This allows 24% of mutant cells to have elevated levels of SOS expression, a percentage similar to that of cells with RecA-green fluorescent protein (RecA-GFP) foci. In an xthA (exonuclease III gene) mutant where there are 3-fold more RecA loading events, recX (a destabilizer of RecA filaments) must be additionally deleted to achieve a population of cells where the percentage having elevated SOS expression (91%) nearly equals the percentage with at least one RecA-GFP focus (83%). It is proposed that, in the xthA mutant, there are three independent mechanisms that repress SOS expression in log-phase cells. These are the rapid processing of RecA filaments by RadA, maintaining the concentration of RecA below a critical level, and the destabilizing of RecA filaments by RecX. Only the first two mechanisms operate independently in a wild-type cell.

Bacterial SOS response: a food safety perspective

NARCIS (Netherlands)

Veen, van der S.; Abee, T.

2011-01-01

The SOS response is a conserved inducible pathway in bacteria that is involved in DNA repair and restart of stalled replication forks. Activation of the SOS response can result in stress resistance and mutagenesis. In food processing facilities and during food preservation, bacteria are exposed to

SOS-projektet

DEFF Research Database (Denmark)

Blomhøj, Morten; Jensen, Tomas Højgaard

2007-01-01

Artiklen beretter om og analyserer det såkaldte SOS-projekt, hvor matematiklærere fra grundskolen, gymnasiet og læreruddannelsen har samarbejdet med matematikdidaktiske forskere om at undersøge og afhjælpe nogle af de udfordringer som danske elever møder i matematik ved overgangen fra grundskole...

On Nash-Equilibria of Approximation-Stable Games

Science.gov (United States)

Awasthi, Pranjal; Balcan, Maria-Florina; Blum, Avrim; Sheffet, Or; Vempala, Santosh

One reason for wanting to compute an (approximate) Nash equilibrium of a game is to predict how players will play. However, if the game has multiple equilibria that are far apart, or ɛ-equilibria that are far in variation distance from the true Nash equilibrium strategies, then this prediction may not be possible even in principle. Motivated by this consideration, in this paper we define the notion of games that are approximation stable, meaning that all ɛ-approximate equilibria are contained inside a small ball of radius Δ around a true equilibrium, and investigate a number of their properties. Many natural small games such as matching pennies and rock-paper-scissors are indeed approximation stable. We show furthermore there exist 2-player n-by-n approximation-stable games in which the Nash equilibrium and all approximate equilibria have support Ω(log n). On the other hand, we show all (ɛ,Δ) approximation-stable games must have an ɛ-equilibrium of support O(Δ^{2-o(1)}/ɛ2{log n}), yielding an immediate n^{O(Δ^{2-o(1)}/ɛ^2log n)}-time algorithm, improving over the bound of [11] for games satisfying this condition. We in addition give a polynomial-time algorithm for the case that Δ and ɛ are sufficiently close together. We also consider an inverse property, namely that all non-approximate equilibria are far from some true equilibrium, and give an efficient algorithm for games satisfying that condition.

Motility of Pseudomonas aeruginosa contributes to SOS-inducible biofilm formation.

Science.gov (United States)

Chellappa, Shakinah T; Maredia, Reshma; Phipps, Kara; Haskins, William E; Weitao, Tao

2013-12-01

DNA-damaging antibiotics such as ciprofloxacin induce biofilm formation and the SOS response through autocleavage of SOS-repressor LexA in Pseudomonas aeruginosa. However, the biofilm-SOS connection remains poorly understood. It was investigated with 96-well and lipid biofilm assays. The effects of ciprofloxacin were examined on biofilm stimulation of the SOS mutant and wild-type strains. The stimulation observed in the wild-type in which SOS was induced was reduced in the mutant in which LexA was made non-cleavable (LexAN) and thus SOS non-inducible. Therefore, the stimulation appeared to involve SOS. The possible mechanisms of inducible biofilm formation were explored by subproteomic analysis of outer membrane fractions extracted from biofilms. The data predicted an inhibitory role of LexA in flagellum function. This premise was tested first by functional and morphological analyses of flagellum-based motility. The flagellum swimming motility decreased in the LexAN strain treated with ciprofloxacin. Second, the motility-biofilm assay was performed, which tested cell migration and biofilm formation. The results showed that wild-type biofilm increased significantly over the LexAN. These results suggest that LexA repression of motility, which is the initial event in biofilm development, contributes to repression of SOS-inducible biofilm formation. Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Exact Solutions of the Field Equations for Empty Space in the Nash Gravitational Theory

Directory of Open Access Journals (Sweden)

Matthew T. Aadne

2017-02-01

Full Text Available John Nash has proposed a new theory of gravity. We define a Nash-tensor equal to the curvature tensor appearing in the Nash field equations for empty space, and calculate its components for two cases: 1. A static, spherically symmetric space; and 2. The expanding, homogeneous and isotropic space of the Friedmann-Lemaitre-Robertson-Walker (FLRW universe models. We find the general, exact solution of Nash’s field equations for empty space in the static case. The line element turns out to represent the Schwarzschild-de Sitter spacetime. Also we find the simplest non-trivial solution of the field equations in the cosmological case, which gives the scale factor corresponding to the de Sitter spacetime. Hence empty space in the Nash theory corresponds to a space with Lorentz Invariant Vacuum Energy (LIVE in the Einstein theory. This suggests that dark energy may be superfluous according to the Nash theory. We also consider a radiation filled universe model in an effort to find out how energy and matter may be incorporated into the Nash theory. A tentative interpretation of the Nash theory as a unified theory of gravity and electromagnetism leads to a very simple form of the field equations in the presence of matter. It should be noted, however, that the Nash theory is still unfinished. A satisfying way of including energy momentum into the theory has yet to be found.

CMOS/SOS processing

Science.gov (United States)

Ramondetta, P.

1980-01-01

Report describes processes used in making complementary - metal - oxide - semiconductor/silicon-on-sapphire (CMOS/SOS) integrated circuits. Report lists processing steps ranging from initial preparation of sapphire wafers to final mapping of "good" and "bad" circuits on a wafer.

SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function

DEFF Research Database (Denmark)

Li, Man; Li, Yong; Weeks, Olivia

2017-01-01

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum...... creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1......associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4×10(-8) by sequence kernel...

Hydrothermal Carbonization of Spent Osmotic Solution (SOS Generated from Osmotic Dehydration of Blueberries

Directory of Open Access Journals (Sweden)

Kaushlendra Singh

2014-09-01

Full Text Available Hydrothermal carbonization of spent osmotic solution (SOS, a waste generated from osmotic dehydration of fruits, has the potential of transformation into hydrochars, a value-added product, while reducing cost and overall greenhouse gas emissions associated with waste disposal. Osmotic solution (OS and spent osmotic solution (SOS generated from the osmotic dehydration of blueberries were compared for their thermo-chemical decomposition behavior and hydrothermal carbonization. OS and SOS samples were characterized for total solids, elemental composition, and thermo-gravimetric analysis (TGA. In addition, hydrothermal carbonization was performed at 250 °C and for 30 min to produce hydrochars. The hydrochars were characterized for elemental composition, Brunauer-Emmett-Teller (BET surface area, particle shape and surface morphology. TGA results show that the SOS sample loses more weight in the lower temperature range than the OS sample. Both samples produced, approximately, 40%–42% (wet-feed basis hydrochar during hydrothermal carbonization but with different properties. The OS sample produced hydrochar, which had spherical particles of 1.79 ± 1.30 μm diameter with a very smooth surface. In contrast, the SOS sample produced hydrochar with no definite particle shape but with a raspberry-like surface.

NOAA NOS SOS, EXPERIMENTAL, 1853-present, Barometric Pressure

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have barometric pressure data. *These services are for testing and...

Mathematical model of the SOS response regulation in wild-type Escherichia coli

International Nuclear Information System (INIS)

Aksenov, S.V.

1997-01-01

Regulation of the SOS response in Escherichia coli, which is a set of inducible cellular reactions introduced after DNA damage, is due to specific interaction of LexA and RecA proteins. LexA protein is a common repressor of the genes of the SOS system, and RecA protein, once transiently activated by the so-called SOS-inducing signal, promotes LexA protein destruction. We have described the SOS regulation by means of differential equations with regard to LexA and RecA concentrations elsewhere. The 'input' function for model equations is the level of the SOS-inducing signal against time. Here we present a means for calculating the concentration of single-stranded DNA (SOS-inducing signal) as a function of time in wild-type cells after ultraviolet irradiation. With model equations one can simulate kinetic curves of SOS regulatory proteins after DNA damage to survey the SOS response kinetics. Simulation of LexA protein kinetics agrees with experimental data. We compare simulated LexA kinetic curves in wild-type and uνr - mutant bacteria, which is useful in investigating the way uνrABC-dependent excision repair modulates the SOS response kinetics. Possible applications of the model to investigating various aspects of the SOS induction are discussed

SOS, the formidable strategy of bacteria against aggressions.

Science.gov (United States)

Baharoglu, Zeynep; Mazel, Didier

2014-11-01

The presence of an abnormal amount of single-stranded DNA in the bacterial cell constitutes a genotoxic alarm signal that induces the SOS response, a broad regulatory network found in most bacterial species to address DNA damage. The aim of this review was to point out that beyond being a repair process, SOS induction leads to a very strong but transient response to genotoxic stress, during which bacteria can rearrange and mutate their genome, induce several phenotypic changes through differential regulation of genes, and sometimes acquire characteristics that potentiate bacterial survival and adaptation to changing environments. We review here the causes and consequences of SOS induction, but also how this response can be modulated under various circumstances and how it is connected to the network of other important stress responses. In the first section, we review articles describing the induction of the SOS response at the molecular level. The second section discusses consequences of this induction in terms of DNA repair, changes in the genome and gene expression, and sharing of genomic information, with their effects on the bacteria's life and evolution. The third section is about the fine tuning of this response to fit with the bacteria's 'needs'. Finally, we discuss recent findings linking the SOS response to other stress responses. Under these perspectives, SOS can be perceived as a powerful bacterial strategy against aggressions. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

NOAA NOS SOS, EXPERIMENTAL, 1853-present, Air Temperature

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have air temperature data. *These services are for testing and evaluation...

NOAA NOS SOS, EXPERIMENTAL, 1853-present, Water Temperature

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have water temperature data. *These services are for testing and evaluation...

Theoretical model of the SOS effect

Energy Technology Data Exchange (ETDEWEB)

Darznek, S A; Mesyats, G A; Rukin, S N; Tsiranov, S N [Russian Academy of Sciences, Ural Division, Ekaterinburg (Russian Federation). Institute of Electrophysics

1997-12-31

Physical principles underlying the operation of semiconductor opening switches (SOS) are highlighted. The SOS effect occurs at a current density of up to 60 kA/cm{sup 2} in silicon p{sup +}-p-n-n{sup +} structures filled with residual electron-hole plasma. Using a theoretical model developed for plasma dynamic calculations, the mechanism by which current passes through the structure at the stage of high conduction and the processes that take place at the stage of current interruption were analyzed. The dynamics of the processes taking place in the structure was calculated with allowance for both diffusive and drift mechanisms of carrier transport. In addition, two recombination types, viz. recombination via impurities and impact Auger recombination, were included in the model. The effect of the structure on the pumping-circuit current and voltage was also taken into account. The real distribution of the doped impurity in the structure and the avalanche mechanism of carrier multiplication were considered. The results of calculations of a typical SOS are presented. The dynamics of the electron-hole plasma is analyzed. It is shown that the SOS effect represents a qualitatively new mechanism of current interruption in semiconductor structures. (author). 4 figs., 7 refs.

NOAA NOS SOS, EXPERIMENTAL, 1853-present, Water Level

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have water surface height above a reference datum. *These services are for...

SNAP/SOS: a package for simulating and analyzing safeguards systems

International Nuclear Information System (INIS)

Grant, F.H. III; Polito, J.; Sabuda, J.

1983-01-01

The effective analysis of safeguards systems at nuclear facilities requires significant effort. The Safeguards Network Analysis Procedure (SNAP) and the SNAP Operating System (SOS) reduce that effort to a manageable level. SNAP provides a detailed analysis of site safeguards for tactical evaluation. SOS helps the analyst organize and manage the SNAP effort effectively. SOS provides a database for model storage, automatic model generation, and computer graphics. The SOS/SNAP combination is a working example of a simulation system including executive-level control, database system, and facilities for model creation, editing, and output analysis

Comparative study of SOS2 and a novel PMP3-1 gene expression in two sunflower (Helianthus annuus L.) lines differing in salt tolerance.

Science.gov (United States)

Saadia, Mubshara; Jamil, Amer; Ashraf, Muhammad; Akram, Nudrat Aisha

2013-06-01

Gene expression pattern of two important regulatory proteins, salt overly sensitive 2 (SOS2) and plasma membrane protein 3-1 (PMP3-1), involved in ion homeostasis, was analyzed in two salinity-contrasting sunflower (Helianthus annuus L.) lines, Hysun-38 (salt tolerant) and S-278 (moderately salt tolerant). The pattern was studied at selected time intervals (24 h) under 150 mM NaCl treatment. Using reverse transcription PCR, SOS2 gene fragment was obtained from young leaf and root tissues of opposing lines while that for PMP3-1 was obtained only from young root tissues. Both tolerant and moderately tolerant lines showed a gradual increase in SOS2 expression in sunflower root tissues. Leaf tissues showed the gradually increasing pattern of SOS2 expression in tolerant plants as compared to that for moderately tolerant ones that showed a relatively lower level of expression for this gene. We found the highest level of PMP 3-1 expression in the roots of tolerant sunflower line at 6 and 12 h postsalinity treatment. The moderately tolerant line showed higher expression of PMP3-1 at 12 and 24 h after salt treatment. Overall, the expression of genes for both the regulator proteins varied significantly in the two sunflower lines differing in salinity tolerance.

SOS reaction kinetics of bacterial cells induced by ultraviolet radiation and α particles

International Nuclear Information System (INIS)

Bonev, M.; Kolev, S.

2000-01-01

It is the purpose of the work to apply the SOS lux test for detecting α particles, as well as to study the SOS system kinetics. Two strains with plasmid pPLS-1 are used: wild type C600 lux and its isogen lysogen with α prophage one. Irradiation is done on dacron nuclear filters. The source of α particles is Am 241 with power 5 Gy/min, and the ultraviolet source - a lamp emitting rays with wave length 254 nm. The light yield is measured by installations made up of scintilometer VA-S-968, High-voltage electric power, and one channel analyzer Strahlugsmessgerat 20046. The SOS lux text is based on the recombinant plasmid pPLS-1 which is a derivative of pBR322 where the lux gene is set under the control of an SOS promoter. E coly recA + strains containing the construction produce considerable amount of photons in the visible zone following treatment with agents damaging the DNA of cells. The kinetic curves of SOS response are obtained after irradiation with α particles and UV rays. DNA damaging agents cause an increase in the initial SOS response rate in the range od smaller doses, and a decrease reaching to block of the one in the high doses range. The light yield of lysogenic cells is lower. As compared to nonelysogene ones. DNA damage caused by α particles are more difficult to repair as compared to pyrimidine dimers. (author)

Induction of the SOS system in Escherichia coli after UVA (320 - 400 nm) irradiation

International Nuclear Information System (INIS)

Batbyamba, G.; Drasil, V.

1988-01-01

Induction of the SOS repair system in E. coli caused by broad-band (320 - 400 nm) UVA radiation and an oxygen effect in this induction were studied using the sfiA::lacZ operon fusion. Moreover, an oxygen effect on the broad-band UVA radiation-induced cell killing was studied. The experiments indicate that: (1) Broad-band UVA light can produce lethal damage to cells as well as DNA damage able to generate an SOS-inducing signal. This damage is O 2 -dependent to a significant extent: SOSIP (O 2 )/ SOSIP (Ar) = 1.61 and OER = 1.96; (2) After UVA irradiation the SOS induction factor increases monotonously in the time interval longer than 4 h indicating that the SOS-inducing DNA damage caused by UVA irradiation has a 'long-lived' character; (3) Oxic and hypoxic incubation following UVA irradiation carried out under aerobic and anaerobic conditions resulted in a strong oxygen effect: SOSIP(O 2 )/SOSIP(Ar) ∼ 5. On the basis of these results and literary data it was concluded that one of the main toxic photoproducts formed as a result of UVA irradiation of the cells in a culture medium might be hydrogen peroxide (H 2 O 2 ). H 2 O 2 decays gradually during post-irradiation incubation and yields reactive radical species, mainly OH radical, that result in a formation of SOS-inducing DNA damages and contribute to cell lethality, and prolonged SOS induction. (author)

The SOS Suicide Prevention Program: Further Evidence of Efficacy and Effectiveness.

Science.gov (United States)

Schilling, Elizabeth A; Aseltine, Robert H; James, Amy

2016-02-01

This study replicated and extended previous evaluations of the Signs of Suicide (SOS) prevention program in a high school population using a more rigorous pre-test post-test randomized control design than used in previous SOS evaluations in high schools (Aseltine and DeMartino 2004; Aseltine et al. 2007). SOS was presented to an ethnically diverse group of ninth grade students in technical high schools in Connecticut. After controlling for the pre-test reports of suicide behaviors, exposure to the SOS program was associated with significantly fewer self-reported suicide attempts in the 3 months following the program. Ninth grade students in the intervention group were approximately 64% less likely to report a suicide attempt in the past 3 months compared with students in the control group. Similarly, exposure to the SOS program resulted in greater knowledge of depression and suicide and more favorable attitudes toward (1) intervening with friends who may be exhibiting signs of suicidal intent and (2) getting help for themselves if they were depressed or suicidal. In addition, high-risk SOS participants, defined as those with a lifetime history of suicide attempt, were significantly less likely to report planning a suicide in the 3 months following the program compared to lower-risk participants. Differential attrition is the most serious limitation of the study; participants in the intervention group who reported a suicide attempt in the previous 3 months at baseline were more likely to be missing at post-test than their counterparts in the control group.

NOAA NDBC SOS, 2008-present, sea_floor_depth_below_sea_surface

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NDBC SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have sea_floor_depth_below_sea_surface data. Because of the nature of SOS...

Metabolically induced liver inflammation leads to NASH and differs from LPS-or IL-1β-induced chronic inflammation

NARCIS (Netherlands)

Liang, W.; Lindeman, J.H.; Menke, A.L.; Koonen, D.P.; Morrison, M.; Havekes, L.M.; Hoek, A.M. van den; Kleemann, R.

2014-01-01

The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1β

Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1 beta-induced chronic inflammation

NARCIS (Netherlands)

Liang, Wen; Lindeman, Jan H.; Menke, Aswin L.; Koonen, Debby P.; Morrison, Martine; Havekes, Louis M.; van den Hoek, Anita M.; Kleemann, Robert

The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1 beta

Nonalcoholic Fatty Liver Disease & NASH

Science.gov (United States)

... Eating, Diet, & Nutrition Clinical Trials Wilson Disease Nonalcoholic Fatty Liver Disease & NASH View or Print All Sections Definition & Facts Nonalcoholic fatty liver disease (NAFLD) is a condition in which fat ...

Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics

Science.gov (United States)

Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen; Christensen, Sune M.; Abel, Steven M.; Iwig, Jeff; Wu, Hung-Jen; Gureasko, Jodi; Rhodes, Christopher; Petit, Rebecca S.; Hansen, Scott D.; Thill, Peter; Yu, Cheng-Han; Stamou, Dimitrios; Chakraborty, Arup K.; Kuriyan, John; Groves, Jay T.

2014-01-01

Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras–guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average. PMID:24994643

Quantum gambling based on Nash-equilibrium

Science.gov (United States)

Zhang, Pei; Zhou, Xiao-Qi; Wang, Yun-Long; Liu, Bi-Heng; Shadbolt, Pete; Zhang, Yong-Sheng; Gao, Hong; Li, Fu-Li; O'Brien, Jeremy L.

2017-06-01

The problem of establishing a fair bet between spatially separated gambler and casino can only be solved in the classical regime by relying on a trusted third party. By combining Nash-equilibrium theory with quantum game theory, we show that a secure, remote, two-party game can be played using a quantum gambling machine which has no classical counterpart. Specifically, by modifying the Nash-equilibrium point we can construct games with arbitrary amount of bias, including a game that is demonstrably fair to both parties. We also report a proof-of-principle experimental demonstration using linear optics.

Adaptive symbiotic organisms search (SOS algorithm for structural design optimization

Directory of Open Access Journals (Sweden)

Ghanshyam G. Tejani

2016-07-01

Full Text Available The symbiotic organisms search (SOS algorithm is an effective metaheuristic developed in 2014, which mimics the symbiotic relationship among the living beings, such as mutualism, commensalism, and parasitism, to survive in the ecosystem. In this study, three modified versions of the SOS algorithm are proposed by introducing adaptive benefit factors in the basic SOS algorithm to improve its efficiency. The basic SOS algorithm only considers benefit factors, whereas the proposed variants of the SOS algorithm, consider effective combinations of adaptive benefit factors and benefit factors to study their competence to lay down a good balance between exploration and exploitation of the search space. The proposed algorithms are tested to suit its applications to the engineering structures subjected to dynamic excitation, which may lead to undesirable vibrations. Structure optimization problems become more challenging if the shape and size variables are taken into account along with the frequency. To check the feasibility and effectiveness of the proposed algorithms, six different planar and space trusses are subjected to experimental analysis. The results obtained using the proposed methods are compared with those obtained using other optimization methods well established in the literature. The results reveal that the adaptive SOS algorithm is more reliable and efficient than the basic SOS algorithm and other state-of-the-art algorithms.

Multiple spinal nerve enlargement and SOS1 mutation: Further evidence of overlap between neurofibromatosis type 1 and Noonan phenotype.

Science.gov (United States)

Santoro, C; Giugliano, T; Melone, M A B; Cirillo, M; Schettino, C; Bernardo, P; Cirillo, G; Perrotta, S; Piluso, G

2018-01-01

Neurofibromatosis type 1 (NF1) has long been considered a well-defined, recognizable monogenic disorder, with neurofibromas constituting a pathognomonic sign. This dogma has been challenged by recent descriptions of patients with enlarged nerves or paraspinal tumors, suggesting that neurogenic tumors and hypertrophic neuropathy may be a complication of Noonan syndrome with multiple lentigines (NSML) or RASopathy phenotype. We describe a 15-year-old boy, whose mother previously received clinical diagnosis of NF1 due to presence of bilateral cervical and lumbar spinal lesions resembling plexiform neurofibromas and features suggestive of NS. NF1 molecular analysis was negative in the mother. The boy presented with Noonan features, multiple lentigines and pectus excavatum. Next-generation sequencing analysis of all RASopathy genes identified p.Ser548Arg missense mutation in SOS1 in the boy, confirmed in his mother. Brain and spinal magnetic resonance imaging scans were negative in the boy. No heart involvement or deafness was observed in proband or mother. This is the first report of a SOS1 mutation associated with hypertrophic neuropathy resembling plexiform neurofibromas, a rare complication in Noonan phenotypes with mutations in RASopathy genes. Our results highlight the overlap between RASopathies, suggesting that NF1 diagnostic criteria need rethinking. Genetic analysis of RASopathy genes should be considered when diagnosis is uncertain. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS complex and perturb RAS signaling.

Science.gov (United States)

Burns, Michael C; Howes, Jennifer E; Sun, Qi; Little, Andrew J; Camper, DeMarco V; Abbott, Jason R; Phan, Jason; Lee, Taekyu; Waterson, Alex G; Rossanese, Olivia W; Fesik, Stephen W

2018-05-01

K-RAS is mutated in approximately 30% of human cancers, resulting in increased RAS signaling and tumor growth. Thus, RAS is a highly validated therapeutic target, especially in tumors of the pancreas, lung and colon. Although directly targeting RAS has proven to be challenging, it may be possible to target other proteins involved in RAS signaling, such as the guanine nucleotide exchange factor Son of Sevenless (SOS). We have previously reported on the discovery of small molecules that bind to SOS1, activate SOS-mediated nucleotide exchange on RAS, and paradoxically inhibit ERK phosphorylation (Burns et al., PNAS, 2014). Here, we describe the discovery of additional, structurally diverse small molecules that also bind to SOS1 in the same pocket and elicit similar biological effects. We tested >160,000 compounds in a fluorescence-based assay to assess their effects on SOS-mediated nucleotide exchange. X-Ray structures revealed that these small molecules bind to the CDC25 domain of SOS1. Compounds that elicited high levels of nucleotide exchange activity in vitro increased RAS-GTP levels in cells, and inhibited phospho ERK levels at higher treatment concentrations. The identification of structurally diverse SOS1 binding ligands may assist in the discovery of new molecules designed to target RAS-driven tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

SOS response and its regulation on the fluoroquinolone resistance.

Science.gov (United States)

Qin, Ting-Ting; Kang, Hai-Quan; Ma, Ping; Li, Peng-Peng; Huang, Lin-Yan; Gu, Bing

2015-12-01

Bacteria can survive fluoroquinolone antibiotics (FQs) treatment by becoming resistant through a genetic change-mutation or gene acquisition. The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation, which is repressed by LexA protein and derepressed by RecA protein. Here, we take a comprehensive review of the SOS gene network and its regulation on the fluoroquinolone resistance. As a unique survival mechanism, SOS may be an important factor influencing the outcome of antibiotic therapy in vivo.

Targeting osteomyelitis with complete [99mTc]besilesomab and fragmented [99mTc]sulesomab antibodies: kinetic evaluations

International Nuclear Information System (INIS)

GRATZ, Stefan; KEMKE, Bendix; KEIZE, Patrik; KAMPEN, Wim U.; LUSTER, Markus; HÖFFKEN, Helmut

2016-01-01

The aim of this retrospective study was to compare the targeting of “pure” osteomyelitis (i.e., without surrounding soft tissue infection) by directly 99mTc-labelled complete immunoglobulin G (IgG) monoclonal antibody (MAb) ([99mTc]besilesomab) and by directly 99mTc-labelled fragment antigen-binding (FAb) MAb ([99mTc]sulesomab) in relation to their kinetic fate. A total of 73 patients with “pure” osteomyelitis were examined with [99mTc]besilesomab, (Scintimun®, IBA/CIS bio international, Saclay, France; N.=38) and [99mTc]sulesomab (LeukoScan®, Immunomedics Inc., Morris Plains, NJ, USA; N.=35). Kinetic data were deduced from whole-body and single-photon emission computed tomographic scans, performed 10 minutes to 24 hour p.i. (region-of-interest technique [ROI]). In targeting “pure” osteomyelitis, sensitivities at 1-4 hours were found to be higher for [99mTc]sulesomab (44% and 80% for [99mTc]besilesomab and [99mTc]sulesomab, respectively) but at significantly lower target/background (T/B) ratios than with [99mTc]besilesomab (1.8±0.3 versus 1.4±0.5 for [99mTc]besilesomab and [99mTc]sulesomab respectively; P<0.01). With [99mTc]besilesomab, there was a continuous osteomyelitis uptake over 24 hours, whereas with [99mTc]sulesomab, the maximal uptake occurred mostly within 1-4 hours, with subsequent clearance being slower for antigen-bound activity than for nonspecific background. Hence, diagnosis was possible mostly after 4h with [99mTc]sulesomab but often not before 24 hours with [99mTc]besilesomab, the later increasing significantly (P<0.01) in sensitivity (87% and 84% for [99mTc]besilesomab and [99mTc]sulesomab, respectively). These results show that the higher sensitivity of [99mTc]sulesomab in osteomyelitis targeting at earlier p.i. times does not rely on an increased antibody uptake but on a more rapid clearance of nonspecific background activity due to faster metabolism and excretion. Intact [99mTc]besilesomab show a slow, continuous uptake

Mapping Modular SOS to Rewriting Logic

DEFF Research Database (Denmark)

Braga, Christiano de Oliveira; Haeusler, Erik Hermann; Meseguer, José

Modular SOS (MSOS) is a framework created to improve the modularity of structural operational semantics specifications, a formalism frequently used in the fields of programming languages semantics and process algebras. With the objective of defining formal tools to support the execution and verif......Modular SOS (MSOS) is a framework created to improve the modularity of structural operational semantics specifications, a formalism frequently used in the fields of programming languages semantics and process algebras. With the objective of defining formal tools to support the execution...

Mapping Modular SOS to Rewriting Logic

DEFF Research Database (Denmark)

Braga, Christiano de Oliveira; Haeusler, Edward Hermann; Meseguer, José

2003-01-01

Modular SOS (MSOS) is a framework created to improve the modularity of structural operational semantics specifications, a formalism frequently used in the fields of programming languages semantics and process algebras. With the objective of defining formal tools to support the execution and verif......Modular SOS (MSOS) is a framework created to improve the modularity of structural operational semantics specifications, a formalism frequently used in the fields of programming languages semantics and process algebras. With the objective of defining formal tools to support the execution...

The Embedding Theorems of Whitney and Nash

Indian Academy of Sciences (India)

IAS Admin

We begin by briefly motivating the idea of a manifold and then discuss the embedding the- orems of Whitney and Nash that allow us to view these objects inside appropriately large Eu- clidean spaces. 1. Introduction. Let us begin by motivating the concept of a manifold. Start with the unit circle C in the plane given by x2.

Nash Equilibria in Fisher Market

Science.gov (United States)

Adsul, Bharat; Babu, Ch. Sobhan; Garg, Jugal; Mehta, Ruta; Sohoni, Milind

Much work has been done on the computation of market equilibria. However due to strategic play by buyers, it is not clear whether these are actually observed in the market. Motivated by the observation that a buyer may derive a better payoff by feigning a different utility function and thereby manipulating the Fisher market equilibrium, we formulate the Fisher market game in which buyers strategize by posing different utility functions. We show that existence of a conflict-free allocation is a necessary condition for the Nash equilibria (NE) and also sufficient for the symmetric NE in this game. There are many NE with very different payoffs, and the Fisher equilibrium payoff is captured at a symmetric NE. We provide a complete polyhedral characterization of all the NE for the two-buyer market game. Surprisingly, all the NE of this game turn out to be symmetric and the corresponding payoffs constitute a piecewise linear concave curve. We also study the correlated equilibria of this game and show that third-party mediation does not help to achieve a better payoff than NE payoffs.

Development of a novel diagnostic algorithm to predict NASH in HCV-positive patients.

Science.gov (United States)

Gallotta, Andrea; Paneghetti, Laura; Mrázová, Viera; Bednárová, Adriana; Kružlicová, Dáša; Frecer, Vladimir; Miertus, Stanislav; Biasiolo, Alessandra; Martini, Andrea; Pontisso, Patrizia; Fassina, Giorgio

2018-05-01

Non-alcoholic steato-hepatitis (NASH) is a severe disease characterised by liver inflammation and progressive hepatic fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that in hepatitis C virus patients steatosis and NASH are associated with faster fibrosis progression and hepatocellular carcinoma. A safe and reliable non-invasive diagnostic method to detect NASH at its early stages is still needed to prevent progression of the disease. We prospectively enrolled 91 hepatitis C virus-positive patients with histologically proven chronic liver disease: 77 patients were included in our study; of these, 10 had NASH. For each patient, various clinical and serological variables were collected. Different algorithms combining squamous cell carcinoma antigen-immunoglobulin-M (SCCA-IgM) levels with other common clinical data were created to provide the probability of having NASH. Our analysis revealed a statistically significant correlation between the histological presence of NASH and SCCA-IgM, insulin, homeostasis model assessment, haemoglobin, high-density lipoprotein and ferritin levels, and smoke. Compared to the use of a single marker, algorithms that combined four, six or seven variables identified NASH with higher accuracy. The best diagnostic performance was obtained with the logistic regression combination, which included all seven variables correlated with NASH. The combination of SCCA-IgM with common clinical data shows promising diagnostic performance for the detection of NASH in hepatitis C virus patients.

New Gastrin Releasing Peptide Receptor-Directed [99mTc]Demobesin 1 Mimics: Synthesis and Comparative Evaluation.

Science.gov (United States)

Nock, Berthold A; Charalambidis, David; Sallegger, Werner; Waser, Beatrice; Mansi, Rosalba; Nicolas, Guillaume P; Ketani, Eleni; Nikolopoulou, Anastasia; Fani, Melpomeni; Reubi, Jean-Claude; Maina, Theodosia

2018-04-12

We have previously reported on the gastrin releasing peptide receptor (GRPR) antagonist [ 99m Tc]1, ([ 99m Tc]demobesin 1, 99m Tc-[N 4 '-diglycolate-dPhe 6 ,Leu-NHEt 13 ]BBN(6-13)). [ 99m Tc]1 has shown superior biological profile compared to analogous agonist-based 99m Tc-radioligands. We herein present a small library of [ 99m Tc]1 mimics generated after structural modifications in (a) the linker ([ 99m Tc]2, [ 99m Tc]3, [ 99m Tc]4), (b) the peptide chain ([ 99m Tc]5, [ 99m Tc]6), and (c) the C-terminus ([ 99m Tc]7 or [ 99m Tc]8). The effects of above modifications on the biological properties of analogs were studied in PC-3 cells and tumor-bearing SCID mice. All analogs showed subnanomolar affinity for the human GRPR, while most receptor-affine 4 and 8 behaved as potent GRPR antagonists in a functional internalization assay. In mice bearing PC-3 tumors, [ 99m Tc]1-[ 99m Tc]6 exhibited GRPR-specific tumor uptake, rapidly clearing from normal tissues. [ 99m Tc]4 displayed the highest tumor uptake (28.8 ± 4.1%ID/g at 1 h pi), which remained high even after 24 h pi (16.3 ± 1.8%ID/g), well surpassing that of [ 99m Tc]1 (5.4 ± 0.7%ID/g at 24 h pi).

STUDY ON NONALCOHOLIC STEATOHEPATITIS (NASH IN PATIENTS OF OBESE, TYPE 2 DIABETES MELLITUS

Directory of Open Access Journals (Sweden)

Uma Shankar Mishra

2018-02-01

Full Text Available BACKGROUND Nonalcoholic steatohepatitis (NASH represents only a part of a wide spectrum of non-alcoholic fatty liver disease (NAFLD and its prevalence is only 2-3% in the general population. Diabetes mellitus increases the risk for severe necroinflammation. The diagnosis rests on the hallmark histological features. Liver biopsy is essential for positive diagnosis and prognostication of NASH. The aim of this study was to evaluate the correlation between NASH and risk factor like diabetes, BMI and other risk factors. MATERIALS AND METHODS 36 patients with histologically confirmed NASH with elevated liver aminotransferase and negative markers for other diseases admitted to our institution from Sept-2012 to August-2014, were included in the study, meeting our inclusion & exclusion criteria. Investigations were done & data was collected. Data were pooled & interpreted using standard statistical methods. RESULTS Twenty out of thirty-six patients had diabetes in our study i.e. 55.6% were diabetes. 22 out of 36 patients i.e. 61.1% had BMI >28 kg/m2 . the mean waist circumference in our study was 93.13 Cm. 15 out of 24 female patients i.e. 62.5% females had WC>88 cm and 8 out of 12 male patients i.e. 66.7% males had WC >102 cm., 20 out of 36 patients i.e. 55.6% patients fulfilled at least 3 out of 5 criteria and therefore had insulin resistance syndrome or metabolic syndrome. CONCLUSION Patients with NASH are typically asymptomatic unless cirrhosis develops. 97.22% patients were dyslipidaemics. NASH may be considered an additional features of insulin resistance & metabolic syndrome. Age, gender, waist circumference, BMI, ALT, AST: ALT ratio, serum triglyceride levels, HTN & BAAT score are independent predictors of NASH.

Data completion problems solved as Nash games

International Nuclear Information System (INIS)

Habbal, A; Kallel, M

2012-01-01

The Cauchy problem for an elliptic operator is formulated as a two-player Nash game. Player (1) is given the known Dirichlet data, and uses as strategy variable the Neumann condition prescribed over the inaccessible part of the boundary. Player (2) is given the known Neumann data, and plays with the Dirichlet condition prescribed over the inaccessible boundary. The two players solve in parallel the associated Boundary Value Problems. Their respective objectives involve the gap between the non used Neumann/Dirichlet known data and the traces of the BVP's solutions over the accessible boundary, and are coupled through a difference term. We prove the existence of a unique Nash equilibrium, which turns out to be the reconstructed data when the Cauchy problem has a solution. We also prove that the completion algorithm is stable with respect to noise, and present two 3D experiments which illustrate the efficiency and stability of our algorithm.

A Noninvasive Score Model for Prediction of NASH in Patients with Chronic Hepatitis B and Nonalcoholic Fatty Liver Disease

Directory of Open Access Journals (Sweden)

Jing Liang

2017-01-01

Full Text Available Aims. To develop a noninvasive score model to predict NASH in patients with combined CHB and NAFLD. Objective and Methods. 65 CHB patients with NAFLD were divided into NASH group (34 patients and non-NASH group (31 patients according to the NAS score. Biochemical indexes, liver stiffness, and Controlled Attenuation Parameter (CAP were determined. Data in the two groups were compared and subjected to multivariate analysis, to establish a score model for the prediction of NASH. Results. In the NASH group, ALT, TG, fasting blood glucose (FBG, M30 CK-18, CAP, and HBeAg positive ratio were significantly higher than in the non-NASH group (P<0.05. Multivariate analysis showed that CK-18 M30, CAP, FBG, and HBVDNA level were independent predictors of NASH. Therefore, a new model combining CK18 M30, CAP, FBG, and HBVDNA level was established using logistic regression. The AUROC curve predicting NASH was 0.961 (95% CI: 0.920–1.00, cutoff value is 0.218, with a sensitivity of 100% and specificity of 80.6%. Conclusion. A noninvasive score model might be considered for the prediction of NASH in patients with CHB combined with NAFLD.

A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH).

Science.gov (United States)

Younossi, Zobair M; Jarrar, Mohammed; Nugent, Clare; Randhawa, Manpreet; Afendy, Mariam; Stepanova, Maria; Rafiq, Nila; Goodman, Zachary; Chandhoke, Vikas; Baranova, Ancha

2008-11-01

Within the spectrum of nonalcoholic fatty liver disease (NAFLD), only patients with nonalcoholic steatohepatitis (NASH) show convincing evidence for progression. To date, liver biopsy remains the gold standard for the diagnosis of NASH; however, liver biopsy is expensive and associated with a small risk, emphasizing the urgent need for noninvasive diagnostic biomarkers. Recent findings suggest a role for apoptosis and adipocytokines in the pathogenesis of NASH. The aim of this study was to develop a noninvasive diagnostic biomarker for NASH. The study included 101 patients with liver biopsies who were tested with enzyme-linked immunosorbent assay (ELISA)-based assays. Of these, 69 were included in the biomarker development set and 32 were included in the biomarker validation set. Clinical data and serum samples were collected at the time of biopsy. Fasting serum samples were assayed for adiponectin, resistin, insulin, glucose, TNF-alpha, IL-6, IL-8, cytokeratin CK-18 (M65 antigen), and caspase-cleaved CK-18 (M30 antigen). Data analysis revealed that the levels of M30 antigen (cleaved CK-18) predicted histological NASH with 70% sensitivity and 83.7% specificity and area under the curve (AUC) = 0.711, p < 10(-4), whereas the predictive value of the levels of intact CK-18 (M65) was higher (63.6% sensitivity and 89.4% specificity and AUC = 0.814, p < 10(-4)). Histological NASH could be predicted by a combination of Cleaved CK-18, a product of the subtraction of Cleaved CK-18 level from intact CK-18 level, serum adiponectin, and serum resistin with a sensitivity of 95.45% sensitivity, specificity of 70.21%, and AUC of 0.908 (p < 10(-4)). Blinded validation of this model confirmed its reliability for separating NASH from simple steatosis. Four ELISA-based tests were combined to form a simple diagnostic biomarker for NASH.

The Nash Equilibrium Revisited: Chaos and Complexity Hidden in Simplicity

Science.gov (United States)

Fellman, Philip V.

The Nash Equilibrium is a much discussed, deceptively complex, method for the analysis of non-cooperative games (McLennan and Berg, 2005). If one reads many of the commonly available definitions the description of the Nash Equilibrium is deceptively simple in appearance. Modern research has discovered a number of new and important complex properties of the Nash Equilibrium, some of which remain as contemporary conundrums of extraordinary difficulty and complexity (Quint and Shubik, 1997). Among the recently discovered features which the Nash Equilibrium exhibits under various conditions are heteroclinic Hamiltonian dynamics, a very complex asymptotic structure in the context of two-player bi-matrix games and a number of computationally complex or computationally intractable features in other settings (Sato, Akiyama and Farmer, 2002). This paper reviews those findings and then suggests how they may inform various market prediction strategies.

SOS - Der kaldes på Smartere Offentlig Styring

DEFF Research Database (Denmark)

Hjortdal, Henrik

2017-01-01

Smartere Offentlig Styring eller SOS. Det var temaet da over hundrede kommunale direktører drøftede offentlig ledelse med en lang række toneangivende danske forskere.......Smartere Offentlig Styring eller SOS. Det var temaet da over hundrede kommunale direktører drøftede offentlig ledelse med en lang række toneangivende danske forskere....

Stent-over-sponge (SOS): a novel technique complementing endosponge therapy for foregut leaks and perforations.

Science.gov (United States)

Valli, Piero V; Mertens, Joachim C; Kröger, Arne; Gubler, Christoph; Gutschow, Christian; Schneider, Paul M; Bauerfeind, Peter

2018-02-01

 Endoluminal vacuum therapy (EVT) has evolved as a promising option for endoscopic treatment of foregut wall injuries in addition to the classic closure techniques using clips or stents. To improve vacuum force and maintain esophageal passage, we combined endosponge treatment with a partially covered self-expandable metal stent (stent-over-sponge; SOS).  Twelve patients with infected upper gastrointestinal wall defects were treated with the SOS technique.  Indications for SOS were anastomotic leakage after surgery (n = 11) and chronic foregut fistula (n = 1). SOS treatment was used as a first-line treatment in seven patients with a success rate of 71.4 % (5/7) and as a second-line treatment after failed previous EVT treatment in five patients (success rate 80 %; 4/5). Overall, SOS treatment was successful in 75 % of patients (9/12). No severe adverse events occurred. CONCLUSION : SOS is an effective method to treat severely infected foregut wall defects in patients where EVT has failed, and also as a first-line treatment. Comparative prospective studies are needed to confirm our preliminary results. © Georg Thieme Verlag KG Stuttgart · New York.

Validation for Vegetation Green-up Date Extracted from GIMMS NDVI and NDVI3g Using Variety of Methods

Science.gov (United States)

Chang, Q.; Jiao, W.

2017-12-01

Phenology is a sensitive and critical feature of vegetation change that has regarded as a good indicator in climate change studies. So far, variety of remote sensing data sources and phenology extraction methods from satellite datasets have been developed to study the spatial-temporal dynamics of vegetation phenology. However, the differences between vegetation phenology results caused by the varies satellite datasets and phenology extraction methods are not clear, and the reliability for different phenology results extracted from remote sensing datasets is not verified and compared using the ground observation data. Based on three most popular remote sensing phenology extraction methods, this research calculated the Start of the growing season (SOS) for each pixels in the Northern Hemisphere for two kinds of long time series satellite datasets: GIMMS NDVIg (SOSg) and GIMMS NDVI3g (SOS3g). The three methods used in this research are: maximum increase method, dynamic threshold method and midpoint method. Then, this study used SOS calculated from NEE datasets (SOS_NEE) monitored by 48 eddy flux tower sites in global flux website to validate the reliability of six phenology results calculated from remote sensing datasets. Results showed that both SOSg and SOS3g extracted by maximum increase method are not correlated with ground observed phenology metrics. SOSg and SOS3g extracted by the dynamic threshold method and midpoint method are both correlated with SOS_NEE significantly. Compared with SOSg extracted by the dynamic threshold method, SOSg extracted by the midpoint method have a stronger correlation with SOS_NEE. And, the same to SOS3g. Additionally, SOSg showed stronger correlation with SOS_NEE than SOS3g extracted by the same method. SOS extracted by the midpoint method from GIMMS NDVIg datasets seemed to be the most reliable results when validated with SOS_NEE. These results can be used as reference for data and method selection in future's phenology study.

Mutational specificity of SOS mutagenesis

International Nuclear Information System (INIS)

Kato, Takeshi

1986-01-01

In an approach to the isolation of mutants of E. coli unable to produce mutations by ultraviolet light, the author has found new umuC-mutants. Their properties could be explained by ''SOS hypothesis of Radman and Witkin'', which has now been justified by many investigators. Analysis of the umuC region of E. coli chromosome cloned in pSK 100 has led to the conclusion that two genes, umuD and umuC, having the capacity of mutation induction express in the same mechanism as that of SOS genes, which is known to be inhibited by LexA protein bonding to ''SOS box'' found at promotor region. Suppressor analysis for mutational specificity has revealed: (i) umuDC-independent mutagens, such as EMS and (oh) 4 Cy, induce selected base substitution alone; and (ii) umuDC-dependent mutagens, such as X-rays and gamma-rays, induce various types of base substitution simultaneously, although they have mutational specificity. In the umuDC-dependent processes of basechange mutagenesis, the spectra of base substitution were a mixture of base substitution reflecting the specific base damages induced by individual mutagens and nonspecific base substitution. In conclusion, base substitution plays the most important role in umuDC-dependent mutagenesis, although mutagenesis of umuDC proteins remains uncertain. (Namekawa, K.)

Advances/applications of MAGIC and SOS

Science.gov (United States)

Warren, Gary; Ludeking, Larry; Nguyen, Khanh; Smithe, David; Goplen, Bruce

1993-12-01

MAGIC and SOS have been applied to investigate a variety of accelerator-related devices. Examples include high brightness electron guns, beam-RF interactions in klystrons, cold-test modes in an RFQ and in RF sources, and a high-quality, flexible, electron gun with operating modes appropriate for gyrotrons, peniotrons, and other RF sources. Algorithmic improvements for PIC have been developed and added to MAGIC and SOS to facilitate these modeling efforts. Two new field algorithms allow improved control of computational numerical noise and selective control of harmonic modes in RF cavities. An axial filter in SOS accelerates simulations in cylindrical coordinates. The recent addition of an export/import feature now allows long devices to be modeled in sections. Interfaces have been added to receive electromagnetic field information from the Poisson group of codes and from EGUN and to send beam information to PARMELA for subsequent tracing of bunches through beam optics. Post-processors compute and display beam properties including geometric, normalized, and slice emittances, and phase-space parameters, and video. VMS, UNIX, and DOS versions are supported, with migration underway toward windows environments.

Thymineless death is inhibited by CsrA in Escherichia coli lacking the SOS response.

Science.gov (United States)

Hamilton, Holly M; Wilson, Ray; Blythe, Martin; Nehring, Ralf B; Fonville, Natalie C; Louis, Edward J; Rosenberg, Susan M

2013-11-01

Thymineless death (TLD) is the rapid loss of colony-forming ability in bacterial, yeast and human cells starved for thymine, and is the mechanism of action of common chemotherapeutic drugs. In Escherichia coli, significant loss of viability during TLD requires the SOS replication-stress/DNA-damage response, specifically its role in inducing the inhibitor of cell division, SulA. An independent RecQ- and RecJ-dependent TLD pathway accounts for a similarly large additional component of TLD, and a third SOS- and RecQ/J-independent TLD pathway has also been observed. Although two groups have implicated the SOS-response in TLD, an SOS-deficient mutant strain from an earlier study was found to be sensitive to thymine deprivation. We performed whole-genome resequencing on that SOS-deficient strain and find that, compared with the SOS-proficient control strain, it contains five mutations in addition to the SOS-blocking lexA(Ind(-)) mutation. One of the additional mutations, csrA, confers TLD sensitivity specifically in SOS-defective strains. We find that CsrA, a carbon storage regulator, reduces TLD in SOS- or SulA-defective cells, and that the increased TLD that occurs in csrA(-) SOS-defective cells is dependent on RecQ. We consider a hypothesis in which the modulation of nucleotide pools by CsrA might inhibit TLD specifically in SOS-deficient (SulA-deficient) cells. Copyright © 2013 Elsevier B.V. All rights reserved.

Nash Stability in Additively Separable Hedonic Games and Community Structures

DEFF Research Database (Denmark)

Olsen, Martin

2009-01-01

  We prove that the problem of deciding whether a Nash stable   partition exists in an Additively Separable Hedonic Game is   NP-complete. We also show that the problem of deciding whether a   non trivial Nash stable partition exists in an   Additively Separable Hedonic Game with   non......-negative and symmetric   preferences is NP-complete. We motivate our study of the   computational complexity by linking Nash stable partitions in   Additively Separable Hedonic Games to community structures in   networks. Our results formally justify that computing community   structures in general is hard....

Inhibitors of LexA Autoproteolysis and the Bacterial SOS Response Discovered by an Academic-Industry Partnership.

Science.gov (United States)

Mo, Charlie Y; Culyba, Matthew J; Selwood, Trevor; Kubiak, Jeffrey M; Hostetler, Zachary M; Jurewicz, Anthony J; Keller, Paul M; Pope, Andrew J; Quinn, Amy; Schneck, Jessica; Widdowson, Katherine L; Kohli, Rahul M

2018-03-09

The RecA/LexA axis of the bacterial DNA damage (SOS) response is a promising, yet nontraditional, drug target. The SOS response is initiated upon genotoxic stress, when RecA, a DNA damage sensor, induces LexA, the SOS repressor, to undergo autoproteolysis, thereby derepressing downstream genes that can mediate DNA repair and accelerate mutagenesis. As genetic inhibition of the SOS response sensitizes bacteria to DNA damaging antibiotics and decreases acquired resistance, inhibitors of the RecA/LexA axis could potentiate our current antibiotic arsenal. Compounds targeting RecA, which has many mammalian homologues, have been reported; however, small-molecules targeting LexA autoproteolysis, a reaction unique to the prokaryotic SOS response, have remained elusive. Here, we describe the logistics and accomplishments of an academic-industry partnership formed to pursue inhibitors against the RecA/LexA axis. A novel fluorescence polarization assay reporting on RecA-induced self-cleavage of LexA enabled the screening of 1.8 million compounds. Follow-up studies on select leads show distinct activity patterns in orthogonal assays, including several with activity in cell-based assays reporting on SOS activation. Mechanistic assays demonstrate that we have identified first-in-class small molecules that specifically target the LexA autoproteolysis step in SOS activation. Our efforts establish a realistic example for navigating academic-industry partnerships in pursuit of anti-infective drugs and offer starting points for dedicated lead optimization of SOS inhibitors that could act as adjuvants for current antibiotics.

Controversies in the Diagnosis and Management of NAFLD and NASH.

Science.gov (United States)

Rinella, Mary E; Loomba, Rohit; Caldwell, Stephen H; Kowdley, Kris; Charlton, Michael; Tetri, Brent; Harrison, Stephen A

2014-04-01

Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of chronic liver disease in the United States. Nonalcoholic steatohepatitis (NASH) occurs in a subset of patients with NAFLD and is characterized by the presence of hepa-tocellular injury, which is progressive in a substantial proportion of cases and can lead to cirrhosis and all of its complications. Although the diagnosis of NAFLD can be made through imaging studies or liver biopsy, the diagnosis of NASH still requires histologic confirmation. Liver biopsy should be performed in the presence of risk factors for advanced disease. Measures aimed at promoting weight loss, a healthier lifestyle, and optimization of metabolic risk factors remain the cornerstone of management of NAFLD. Therapeutic agents that are presently considered the most promising in NAFLD are effective in less than 50% of patients. Among patients with biopsy-proven NASH, treatment with pharmacologic agents should be considered; however, the role of specific agents in NASH still needs further study. Despite a wealth of research over the past 15 years, many controversies remain with respect to the diagnosis and management of NAFLD and NASH as well as the influence of alcohol on liver disease progression in these patients.

Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression

Science.gov (United States)

Guo, Liang; Chen, Zhimin; Xia, Houjun; Li, Siming; Zhang, Yanqiao; Kobberup, Sune; Zou, Weiping; Lin, Jiandie D.

2017-01-01

Nonalcoholic steatohepatitis (NASH) is characterized by progressive liver injury, inflammation, and fibrosis; however, the mechanisms that govern the transition from hepatic steatosis, which is relatively benign, to NASH remain poorly defined. Neuregulin 4 (Nrg4) is an adipose tissue–enriched endocrine factor that elicits beneficial metabolic effects in obesity. Here, we show that Nrg4 is a key component of an endocrine checkpoint that preserves hepatocyte health and counters diet-induced NASH in mice. Nrg4 deficiency accelerated liver injury, fibrosis, inflammation, and cell death in a mouse model of NASH. In contrast, transgenic expression of Nrg4 in adipose tissue alleviated diet-induced NASH. Nrg4 attenuated hepatocyte death in a cell-autonomous manner by blocking ubiquitination and proteasomal degradation of c-FLIPL, a negative regulator of cell death. Adeno-associated virus–mediated (AAV-mediated) rescue of hepatic c-FLIPL expression in Nrg4-deficent mice functionally restored the brake for steatosis to NASH transition. Thus, hepatic Nrg4 signaling serves as an endocrine checkpoint for steatosis-to-NASH progression by activating a cytoprotective pathway to counter stress-induced liver injury. PMID:29106384

Suppression of the E. coli SOS response by dNTP pool changes.

Science.gov (United States)

Maslowska, Katarzyna H; Makiela-Dzbenska, Karolina; Fijalkowska, Iwona J; Schaaper, Roel M

2015-04-30

The Escherichia coli SOS system is a well-established model for the cellular response to DNA damage. Control of SOS depends largely on the RecA protein. When RecA is activated by single-stranded DNA in the presence of a nucleotide triphosphate cofactor, it mediates cleavage of the LexA repressor, leading to expression of the 30(+)-member SOS regulon. RecA activation generally requires the introduction of DNA damage. However, certain recA mutants, like recA730, bypass this requirement and display constitutive SOS expression as well as a spontaneous (SOS) mutator effect. Presently, we investigated the possible interaction between SOS and the cellular deoxynucleoside triphosphate (dNTP) pools. We found that dNTP pool changes caused by deficiencies in the ndk or dcd genes, encoding nucleoside diphosphate kinase and dCTP deaminase, respectively, had a strongly suppressive effect on constitutive SOS expression in recA730 strains. The suppression of the recA730 mutator effect was alleviated in a lexA-deficient background. Overall, the findings suggest a model in which the dNTP alterations in the ndk and dcd strains interfere with the activation of RecA, thereby preventing LexA cleavage and SOS induction. Published by Oxford University Press on behalf of Nucleic Acids Research 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

[99mTc[TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent

International Nuclear Information System (INIS)

Kung Meiping; Stevenson, D.A.; Ploessl, K.; Meegalla, S.K.; Beckwith, A.; Essman, W.D.; Mu, M.; Lucki, I.; Kung, H.F.

1997-01-01

Technetium-99m is the most commonly used radionuclide in routine nuclear medicine imaging procedures. Development of 99m Tc-labeled receptor-specific imaging agents for studying the central nervous system is potentially useful for evaluation of brain function in normal and disease states. A novel 99m Tc-labeled tropane derivative, [ 99m Tc[TRODAT-1, which is useful as a potential CNS dopamine transporter imaging agent, was evaluated and characterized. After i.v. injection into rats, [ 99m Tc[TRODAT-1 displayed specific brain uptake in the rat striatal region (striatum-cerebellum/cerebellum ratio 1.8 at 60 min), where dopamine neurons are concentrated. The specific striatal uptake could be blocked by pretreating rats with a dose of competing dopamine transporter ligand, β-CIT (or RTI-55, i.v., 1 mg/kg). However, the specific striatal uptake of [ 99m Tc[TRODAT-1 was not affected by co-injection of excess free ligand (TRODAT-1, up to 200 μg per rat) or by pretreating the rats with haloperidol (i.v., 1 mg/kg). The specific uptake in striatal regions of rats that had prior 6-hydroxydopamine lesion in the substantia nigra area showed a dramatic reduction. The radioactive material recovered from the rat striatal homogenates at 60 min after i.v. injection of [ 99m Tc[TRODAT-1 showed primarily the original compound (>95%), a good indication of in vivo stability in brain tissue. Similar and comparable organ distribution patterns and brain regional uptakes of [ 99m Tc[TRODAT-1 were obtained for male and female rats. (orig./AJ). With 4 figs., 6 tabs

Nash equilibrium with lower probabilities

DEFF Research Database (Denmark)

Groes, Ebbe; Jacobsen, Hans Jørgen; Sloth, Birgitte

1998-01-01

We generalize the concept of Nash equilibrium in mixed strategies for strategic form games to allow for ambiguity in the players' expectations. In contrast to other contributions, we model ambiguity by means of so-called lower probability measures or belief functions, which makes it possible...

Systematically Altering Bacterial SOS Activity under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics.

Science.gov (United States)

Mo, Charlie Y; Manning, Sara A; Roggiani, Manuela; Culyba, Matthew J; Samuels, Amanda N; Sniegowski, Paul D; Goulian, Mark; Kohli, Rahul M

2016-01-01

The bacterial SOS response is a DNA damage repair network that is strongly implicated in both survival and acquired drug resistance under antimicrobial stress. The two SOS regulators, LexA and RecA, have therefore emerged as potential targets for adjuvant therapies aimed at combating resistance, although many open questions remain. For example, it is not well understood whether SOS hyperactivation is a viable therapeutic approach or whether LexA or RecA is a better target. Furthermore, it is important to determine which antimicrobials could serve as the best treatment partners with SOS-targeting adjuvants. Here we derived Escherichia coli strains that have mutations in either lexA or recA genes in order to cover the full spectrum of possible SOS activity levels. We then systematically analyzed a wide range of antimicrobials by comparing the mean inhibitory concentrations (MICs) and induced mutation rates for each drug-strain combination. We first show that significant changes in MICs are largely confined to DNA-damaging antibiotics, with strains containing a constitutively repressed SOS response impacted to a greater extent than hyperactivated strains. Second, antibiotic-induced mutation rates were suppressed when SOS activity was reduced, and this trend was observed across a wider spectrum of antibiotics. Finally, perturbing either LexA or RecA proved to be equally viable strategies for targeting the SOS response. Our work provides support for multiple adjuvant strategies, while also suggesting that the combination of an SOS inhibitor with a DNA-damaging antibiotic could offer the best potential for lowering MICs and decreasing acquired drug resistance. IMPORTANCE Our antibiotic arsenal is becoming depleted, in part, because bacteria have the ability to rapidly adapt and acquire resistance to our best agents. The SOS pathway, a widely conserved DNA damage stress response in bacteria, is activated by many antibiotics and has been shown to play central role in

Analysis of the SOS response of Vibrio and other bacteria with multiple chromosomes

Directory of Open Access Journals (Sweden)

Sanchez-Alberola Neus

2012-02-01

Full Text Available Abstract Background The SOS response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. Results Our analysis provides the first comprehensive description of the SOS response in a family (Vibrionaceae that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. Conclusions Our findings confirm that the SOS response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS response plays an

Analysis of the SOS response of Vibrio and other bacteria with multiple chromosomes.

Science.gov (United States)

Sanchez-Alberola, Neus; Campoy, Susana; Barbé, Jordi; Erill, Ivan

2012-02-03

The SOS response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. Our analysis provides the first comprehensive description of the SOS response in a family (Vibrionaceae) that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. Our findings confirm that the SOS response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS response plays an essential role in these organisms and sheds light into the

22 CFR 99.1 - Definitions.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Definitions. 99.1 Section 99.1 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED SERVICES REPORTING ON CONVENTION AND NON-CONVENTION ADOPTIONS OF EMIGRATING CHILDREN § 99.1 Definitions. As used in this part, the term: (a) Convention means...

Long-term Nash equilibria in electricity markets

International Nuclear Information System (INIS)

Pozo, David; Contreras, Javier; Caballero, Angel; de Andres, Antonio

2011-01-01

In competitive electricity markets, companies simultaneously offer their productions to obtain the maximum profits on a daily basis. In the long run, the strategies utilized by the electric companies lead to various long-term equilibria that can be analyzed with the appropriate tools. We present a methodology to find plausible long-term Nash equilibria in pool-based electricity markets. The methodology is based on an iterative market Nash equilibrium model in which the companies can decide upon their offer strategies. An exponential smoothing of the bids submitted by the companies is applied to facilitate the convergence of the iterative procedure. In each iteration of the model the companies face residual demand curves that are accurately modeled by Hermite interpolating polynomials. We introduce the concept of meta-game equilibrium strategies to allow companies to have a range of offer strategies where several pure and mixed meta-game Nash equilibria are possible. With our model it is also possible to model uncertainty or to generate price scenarios for financial models that assess the value of a generating unit by real options analysis. The application of the proposed methodology is illustrated with several realistic case studies. (author)

Nash Equilibria in Symmetric Games with Partial Observation

DEFF Research Database (Denmark)

Bouyer, Patricia; Markey, Nicolas; Vester, Steen

2014-01-01

We investigate a model for representing large multiplayer games, which satisfy strong symmetry properties. This model is made of multiple copies of an arena; each player plays in his own arena, and can partially observe what the other players do. Therefore, this game has partial information...... and symmetry constraints, which make the computation of Nash equilibria difficult. We show several undecidability results, and for bounded-memory strategies, we precisely characterize the complexity of computing pure Nash equilibria (for qualitative objectives) in this game model....

21 CFR 99.1 - Scope.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Scope. 99.1 Section 99.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL DISSEMINATION OF INFORMATION ON UNAPPROVED/NEW USES FOR MARKETED DRUGS, BIOLOGICS, AND DEVICES General Information § 99.1 Scope. (a) This...

Construct Validity of the Societal Outreach Scale (SOS).

Science.gov (United States)

Fike, David S; Denton, Jason; Walk, Matt; Kish, Jennifer; Gorman, Ira

2018-04-01

The American Physical Therapy Association (APTA) has been working toward a vision of increasing professional focus on societal-level health. However, performance of social responsibility and related behaviors by physical therapists remain relatively poorly integrated into practice. Promoting a focus on societal outreach is necessary for all health care professionals to impact the health of their communities. The objective was to document the validity of the 14-item Societal Outreach Scale (SOS) for use with practicing physical therapists. This study used a cross-sectional survey. The SOS was transmitted via email to all therapists who were licensed and practicing in 10 states in the United States that were purposefully selected to assure a broad representation. A sample of 2612 usable responses was received. Factor analysis was applied to assess construct validity of the instrument. Of alternate models, a 3-factor model best demonstrated goodness of fit with the sample data according to conventional indices (standardized root mean squared residual = .03, comparative fit index .96, root mean square error of approximation = .06). The 3 factors measured by the SOS were labeled Societal-Level Health Advocacy, Community Engagement/Social Integration, and Political Engagement. Internal consistency reliability was 0.7 for all factors. The 3-factor SOS demonstrated acceptable validity and reliability. Though the sample included a broad representation of physical therapists, this was a single cross-sectional study. Additional confirmatory factor analysis, reliability testing, and word refinement of the tool are warranted. Given the construct validity and reliability of the 3-factor SOS, it is recommended for use as a validated instrument to measure physical therapists' performance of social responsibility and related behaviors.

A metabonomic evaluation of the monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats

International Nuclear Information System (INIS)

Conotte, R.; Colet, J.-M.

2014-01-01

The main curative treatment of colorectal cancer remains the surgery. However, when metastases are suspected, surgery is followed by a preventive chemotherapy using oxaliplatin which, unfortunately, may cause liver sinusoidal obstruction syndrome (SOS). Such hepatic damage is barely detected during or after chemotherapy due to a lack of effective diagnostic procedures, but liver biopsy. The primary objective of the present study was to identify potential early diagnosis biomarkers of SOS using a metabonomic approach. SOS was induced in rats by monocrotaline, a prototypical toxic substance. 1 H NMR spectroscopy analysis of urine samples collected from rats treated with monocrotaline showed significant metabolic changes as compared to controls. During a first phase, cellular protective mechanisms such as an increased synthesis of GSH (reduced taurine) and the recruitment of cell osmolytes in the liver (betaine) were seen. In the second phase, the disturbance of the urea cycle (increased ornithine and urea reduction) leading to the depletion of NO, the alteration in the GSH synthesis (increased creatine and GSH precursors (glutamate, dimethylglycine and sarcosine)), and the liver necrosis (decrease taurine and increase creatine) all indicate the development of SOS. - Highlights: • Urine metabonomic profiles of SOS have been identified. • Urine osmoprotectants and anti-oxidants indicated an initial liver protection. • Liver necrosis was demonstrated by increased urine levels of taurine and creatine. • NO depletion was suggested by changes in ornithine and urea

Bevacizumab exacerbates sinusoidal obstruction syndrome (SOS) in the animal model and increases MMP 9 production.

Science.gov (United States)

Jafari, Azin; Matthaei, Hanno; Wehner, Sven; Tonguc, Tolga; Kalff, Jörg C; Manekeller, Steffen

2018-04-24

Thanks to modern multimodal treatment the ouctome of patients with colorectal cancer has experienced significant improvements. As a downside, agent specific side effects have been observed such as sinusoidal obstruction syndrome (SOS) after oxaliplatin chemotherapy (OX). Bevazicumab targeting VEGF is nowadays comprehensively used in combination protocols with OX but its impact on hepatotoxicity is thus far elusive and focus of the present study. After MCT administration 67% of animals developed SOS. GOT serum concentration significantly increased in animals developing SOS ( p SOS. In contrast, animals receiving VEGF developed SOS merely in 40% while increasing the VEGF dose led to a further decrease in SOS development to 25%. MMP 9 concentration in animals developing SOS was significantly higher compared to controls ( p SOS paralleled by MMP 9 production. Therefore, OX-Bevacizumab combination therapies should be administered with caution, especially if liver parenchyma damage is apparent. Male Sprague-Dawley rats were gavaged Monocrotaline (MCT) to induce SOS. Recombinant VEGF or an Anti-VEGF antibody was administered to MCT-treated rats and the hepatotoxic effect monitored in defined time intervals. MMP 9 expression in the liver was measured by ELISA.

A flow cytometry-optimized assay using an SOS-green fluorescent protein (SOS-GFP) whole-cell biosensor for the detection of genotoxins in complex environments

DEFF Research Database (Denmark)

Norman, Anders; Hansen, Lars H.; Sørensen, Søren Johannes

2006-01-01

/mL, and proved far more sensitive than a previously published assay using the same biosensor strain. By applying the SOS-green fluorescent protein (GFP) whole-cell biosensor directly to soil microcosms we were also able to evaluate both the applicability and sensitivity of a biosensor based on SOS...

[{sup 99m}Tc]TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent

Energy Technology Data Exchange (ETDEWEB)

Meiping, Kung [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Stevenson, D A [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Ploessl, K [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Meegalla, S K [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Beckwith, A [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Essman, W D [Department of Psychiatry, University of Pennsylvania, Philadelphia (United States); Mu, M [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Lucki, I [Department of Psychiatry, University of Pennsylvania, Philadelphia (United States); [Department of Pharmacology, University of Pennsylvania, Philadelphia (United States); Kung, H F [Department of Radiology, University of Pennsylvania, Philadelphia (United States); [Department of Pharmacology, University of Pennsylvania, Philadelphia (United States)

1997-04-01

Technetium-99m is the most commonly used radionuclide in routine nuclear medicine imaging procedures. Development of {sup 99m}Tc-labeled receptor-specific imaging agents for studying the central nervous system is potentially useful for evaluation of brain function in normal and disease states. A novel {sup 99m}Tc-labeled tropane derivative, [{sup 99m}Tc]TRODAT-1, which is useful as a potential CNS dopamine transporter imaging agent, was evaluated and characterized. After i.v. injection into rats, [{sup 99m}Tc]TRODAT-1 displayed specific brain uptake in the rat striatal region (striatum-cerebellum/cerebellum ratio 1.8 at 60 min), where dopamine neurons are concentrated. The specific striatal uptake could be blocked by pretreating rats with a dose of competing dopamine transporter ligand, {beta}-CIT (or RTI-55, i.v., 1 mg/kg). However, the specific striatal uptake of [{sup 99m}Tc]TRODAT-1 was not affected by co-injection of excess free ligand (TRODAT-1, up to 200 {mu}g per rat) or by pretreating the rats with haloperidol (i.v., 1 mg/kg). The specific uptake in striatal regions of rats that had prior 6-hydroxydopamine lesion in the substantia nigra area showed a dramatic reduction. The radioactive material recovered from the rat striatal homogenates at 60 min after i.v. injection of [{sup 99m}Tc]TRODAT-1 showed primarily the original compound (>95%), a good indication of in vivo stability in brain tissue. Similar and comparable organ distribution patterns and brain regional uptakes of [{sup 99m}Tc]TRODAT-1 were obtained for male and female rats. (orig./AJ). With 4 figs., 6 tabs.

Molecular kinetics. Ras activation by SOS: allosteric regulation by altered fluctuation dynamics.

Science.gov (United States)

Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen; Christensen, Sune M; Abel, Steven M; Iwig, Jeff; Wu, Hung-Jen; Gureasko, Jodi; Rhodes, Christopher; Petit, Rebecca S; Hansen, Scott D; Thill, Peter; Yu, Cheng-Han; Stamou, Dimitrios; Chakraborty, Arup K; Kuriyan, John; Groves, Jay T

2014-07-04

Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras-guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average. Copyright © 2014, American Association for the Advancement of Science.

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest.

Science.gov (United States)

Duran, Leidy Tatiana Díaz; Rincón, Nathalia Olivar; Galvis, Carlos Eduardo Puerto; Kouznetsov, Vladimir V; Lorenzo, Jorge Luis Fuentes

2015-03-01

Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4-methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C-2 substitution with α-, β-, or γ-pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure-genotoxicity relationships and bioassay-guided quinoline synthesis. © 2013 Wiley Periodicals, Inc.

Phosphine reduced IgG. A new method for 99mTc labeling immunoglobulins

International Nuclear Information System (INIS)

Arteaga de Murphy, C.; Melendez-Alafort, L.; Martinez-Rivero, O.; Gomez, E.; Ferro-Flores, G.

1997-01-01

A new technetium labeling method for immunoglobulins reduced with tris(2-carboxy-ethyl)phosphine hydrochloride is presented. The Sandoglobulina IgG source was assayed for purity and optimum reagent's concentration and incubation times were determined. It was purified by column chromatography and labelled with Sn 2+ reduced technetium in the presence of MDP. The kit is easy to prepare, labeling efficiency is >(97±1.9)% and stable for 6 hours.The immunoreactivity of the 99 Tc-IgG was verified by electrophoresis and Western blot tests. The IgG retained its structure after both the reducing and labeling processes and it was the only labeled species. (author)

Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

Science.gov (United States)

Bunnell, Bryan E; Escobar, Jillian F; Bair, Kirsten L; Sutton, Mark D; Crane, John K

2017-01-01

Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx) and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

Directory of Open Access Journals (Sweden)

Bryan E Bunnell

Full Text Available Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions.

Science.gov (United States)

Beneteau, Claire; Cavé, Hélène; Moncla, Anne; Dorison, Nathalie; Munnich, Arnold; Verloes, Alain; Leheup, Bruno

2009-10-01

We report five cases of multiple giant cell lesions in patients with typical Noonan syndrome. Such association has frequently been referred to as Noonan-like/multiple giant cell (NL/MGCL) syndrome before the molecular definition of Noonan syndrome. Two patients show mutations in PTPN11 (p.Tyr62Asp and p.Asn308Asp) and three in SOS1 (p.Arg552Ser and p.Arg552Thr). The latter are the first SOS1 mutations reported outside PTPN11 in NL/MGCL syndrome. MGCL lesions were observed in jaws ('cherubism') and joints ('pigmented villonodular synovitis'). We show through those patients that both types of MGCL are not PTPN11-specific, but rather represent a low penetrant (or perhaps overlooked) complication of the dysregulated RAS/MAPK signaling pathway. We recommend discarding NL/MGCL syndrome from the nosology, as this presentation is neither gene-nor allele-specific of Noonan syndrome; these patients should be described as Noonan syndrome with MGCL (of the mandible, the long bone...). The term cherubism should be used only when multiple giant cell lesions occur without any other clinical and molecular evidence of Noonan syndrome, with or without mutations of the SH3BP2 gene.

Equilibrio de Nash y resolución de conflictos

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Maritza Vanegas de Medina

2014-01-01

Full Text Available En el presente artículo, se introduce la noción de juegos suma-cero construida a partir de las teorías de von Neumann y Morgenstern (1953 sus propiedades básicas y algunos ejemplos elaborados a partir del lenguaje matemático, para explicar a la luz de las teorías de Nash (1950 las estrategias usadas por los jugadores en el contexto económico, militar y social. También, se presenta la noción de juego suma no-cero, no cooperativos entre dos personas, asumiendo la continuidad diferenciable de la función de pago. Finalmente, se explica a través de ejemplos construidos por los autores, los métodos de determinación del equilibrio de Nash puro y una metodología elemental para la determinación del equilibrio de Nash mixto.

Congruence for SOS with data

NARCIS (Netherlands)

Mousavi, M.R.; Reniers, M.A.; Groote, J.F.

2004-01-01

Abstract While studying the specification of the operational semantics of different programming languages and formalisms, one can observe the following three facts. Firstly, Plotkin¿s style of Structured Operational Semantics (SOS) has become a standard in defining operational semantics. Secondly,

Dynamic studies of H-Ras•GTPγS interactions with nucleotide exchange factor Sos reveal a transient ternary complex formation in solution.

Science.gov (United States)

Vo, Uybach; Vajpai, Navratna; Embrey, Kevin J; Golovanov, Alexander P

2016-07-14

The cycling between GDP- and GTP- bound forms of the Ras protein is partly regulated by the binding of Sos. The structural/dynamic behavior of the complex formed between activated Sos and Ras at the point of the functional cycle where the nucleotide exchange is completed has not been described to date. Here we show that solution NMR spectra of H-Ras∙GTPγS mixed with a functional fragment of Sos (Sos(Cat)) at a 2:1 ratio are consistent with the formation of a rather dynamic assembly. H-Ras∙GTPγS binding was in fast exchange on the NMR timescale and retained a significant degree of molecular tumbling independent of Sos(Cat), while Sos(Cat) also tumbled largely independently of H-Ras. Estimates of apparent molecular weight from both NMR data and SEC-MALS revealed that, at most, only one H-Ras∙GTPγS molecule appears stably bound to Sos. The weak transient interaction between Sos and the second H-Ras∙GTPγS may provide a necessary mechanism for complex dissociation upon the completion of the native GDP → GTP exchange reaction, but also explains measurable GTP → GTP exchange activity of Sos routinely observed in in vitro assays that use fluorescently-labelled analogs of GTP. Overall, the data presents the first dynamic snapshot of Ras functional cycle as controlled by Sos.

Revision to DOE Order 450.1 [1] and How it affects DOE Sites

International Nuclear Information System (INIS)

Birchfield, J.W.

2009-01-01

On June 4, 2008, DOE finalized the latest technical revision of DOE Order 450.1A. The latest revision of the order contains many new EMS requirements that can have a dramatic effect on what and how activities are conducted at the various DOE sites. The latest revision of the order contains many new Environmental Management System (EMS) requirements that can have a dramatic effect on what and how activities are conducted at the various DOE sites. DOE Order 450.1 contains some major technical revisions that will directly affect each DOE site. The exact extent of the changes to the order will vary at each site depending on the status of EMS implementation utilizing the ISO 14001:2004 (2004 denotes the latest version in effect) Standard and Executive Order 13423. ISO 14001:2004 contains a total of 17 elements (i.e., requirements) that are required for EMS programs. Because the original DOE Order 450.1 did not require conformance to the original ISO 14001:1996 Standard, this is a significant addition to EMS program management. Some EMS program elements will require effort, some significant, depending upon the complexity of the operations conducted at the various DOE sites. Significant EMS elements added include audit programs (e.g., internal and external), operational controls (e.g., procedures, personnel and equipment), monitoring and measurement (e.g., key environmental metrics tracking and equipment calibration), document controls, communication and preventive actions. DOE has also drastically altered its approach to sustainable development and environmental stewardship by specifying departmental goals through: - Reduction or elimination of the toxicity of waste through pollution prevention; - Reduction or elimination of the acquisition, use and release of toxic/hazardous materials and chemicals; - Maximizing the purchase of environmental friendly chemicals and materials in the conduct of operations; - Reduction or elimination of environmental impacts from electronic

A metabonomic evaluation of the monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats

Energy Technology Data Exchange (ETDEWEB)

Conotte, R.; Colet, J.-M., E-mail: jean-marie.colet@umons.ac.be

2014-04-15

The main curative treatment of colorectal cancer remains the surgery. However, when metastases are suspected, surgery is followed by a preventive chemotherapy using oxaliplatin which, unfortunately, may cause liver sinusoidal obstruction syndrome (SOS). Such hepatic damage is barely detected during or after chemotherapy due to a lack of effective diagnostic procedures, but liver biopsy. The primary objective of the present study was to identify potential early diagnosis biomarkers of SOS using a metabonomic approach. SOS was induced in rats by monocrotaline, a prototypical toxic substance. {sup 1}H NMR spectroscopy analysis of urine samples collected from rats treated with monocrotaline showed significant metabolic changes as compared to controls. During a first phase, cellular protective mechanisms such as an increased synthesis of GSH (reduced taurine) and the recruitment of cell osmolytes in the liver (betaine) were seen. In the second phase, the disturbance of the urea cycle (increased ornithine and urea reduction) leading to the depletion of NO, the alteration in the GSH synthesis (increased creatine and GSH precursors (glutamate, dimethylglycine and sarcosine)), and the liver necrosis (decrease taurine and increase creatine) all indicate the development of SOS. - Highlights: • Urine metabonomic profiles of SOS have been identified. • Urine osmoprotectants and anti-oxidants indicated an initial liver protection. • Liver necrosis was demonstrated by increased urine levels of taurine and creatine. • NO depletion was suggested by changes in ornithine and urea.

Refined functional relations for the elliptic SOS model

Energy Technology Data Exchange (ETDEWEB)

Galleas, W., E-mail: w.galleas@uu.nl [ARC Centre of Excellence for the Mathematics and Statistics of Complex Systems, University of Melbourne, VIC 3010 (Australia)

2013-02-21

In this work we refine the method presented in Galleas (2012) [1] and obtain a novel kind of functional equation determining the partition function of the elliptic SOS model with domain wall boundaries. This functional relation arises from the dynamical Yang-Baxter relation and its solution is given in terms of multiple contour integrals.

Refined functional relations for the elliptic SOS model

International Nuclear Information System (INIS)

Galleas, W.

2013-01-01

In this work we refine the method presented in Galleas (2012) [1] and obtain a novel kind of functional equation determining the partition function of the elliptic SOS model with domain wall boundaries. This functional relation arises from the dynamical Yang–Baxter relation and its solution is given in terms of multiple contour integrals.

NASH Therapy: omega 3 supplementation, vitamin E, insulin sensitizers and statin drugs

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Stephen Caldwell

2017-06-01

Full Text Available Non-alcoholic steatohepatitis (NASH is the more aggressive form of non-alcoholic fatty liver disease (NAFLD. NASH can progress to hepatic fibrosis, cirrhosis, portal hypertension and primary liver cancer. Therapy is evolving with a substantial number of trials of promising new agents now in progress. In this article however, we will examine data for several older forms of therapy which have been fairly extensively studied over the years: Polyunsaturated Fatty Acid (PUFA supplements, vitamin E, insulin sensitizing agents with a focus on pioglitazone and statin agents. Early interest in PUFA derived from their potential benefit in cardio-metabolic disease and the close association of NAFLD/NASH with Metabolic Syndrome. Results have been variable although most studies show reduction of liver fat without other major effects and their effects are influenced by concomitant weight loss and underlying genetic factors. Vitamin E has had some efficacy in pediatric NASH but questionable efficacy in even mild NASH among adults. Pioglitazone has shown significant histological benefit in a number of trials but concern over side-effects (especially weight gain have dampened enthusiasm. A newer insulin sensitizer, liraglutide, has also shown promise in a small randomized, controlled trial. Very limited data exists regarding the histological effects of the statins in NASH and these agents appear to be fairly neutral with neither clear cut benefit nor detriment. Their use is best guided by cardiovascular risks rather than liver histology.

Prohibitin-induced, obesity-associated insulin resistance and accompanying low-grade inflammation causes NASH and HCC.

Science.gov (United States)

Ande, Sudharsana R; Nguyen, K Hoa; Grégoire Nyomba, B L; Mishra, Suresh

2016-03-23

Obesity increases the risk for nonalcoholic steatohepatitis (NASH) and hepatocarcinogenesis. However, the underlying mechanisms involved in the disease process remain unclear. Recently, we have developed a transgenic obese mouse model (Mito-Ob) by prohibitin mediated mitochondrial remodeling in adipocytes. The Mito-Ob mice develop obesity in a sex-neutral manner, but obesity-associated adipose inflammation and metabolic dysregulation in a male sex-specific manner. Here we report that with aging, the male Mito-Ob mice spontaneously develop obesity-linked NASH and hepatocellular carcinoma (HCC). In contrast, the female Mito-Ob mice maintained normal glucose and insulin levels and did not develop NASH and HCC. The anti-inflammatory peptide ghrelin was significantly upregulated in the female mice and down regulated in the male mice compared with respective control mice. In addition, a reduction in the markers of mitochondrial content and function was found in the liver of male Mito-Ob mice with NASH/HCC development. We found that ERK1/2 signaling was significantly upregulated whereas STAT3 signaling was significantly down regulated in the tumors from Mito-Ob mice. These data provide a proof-of-concept that the metabolic and inflammatory status of the adipose tissue and their interplay at the systemic and hepatic level play a central role in the pathogenesis of obesity-linked NASH and HCC.

Radiation-hardened CMOS/SOS LSI circuits

International Nuclear Information System (INIS)

Aubuchon, K.G.; Peterson, H.T.; Shumake, D.P.

1976-01-01

The recently developed technology for building radiation-hardened CMOS/SOS devices has now been applied to the fabrication of LSI circuits. This paper describes and presents results on three different circuits: an 8-bit adder/subtractor (Al gate), a 256-bit shift register (Si gate), and a polycode generator (Al gate). The 256-bit shift register shows very little degradation after 1 x 10 6 rads (Si), with an increase from 1.9V to 2.9V in minimum operating voltage, a decrease of about 20% in maximum frequency, and little or no change in quiescent current. The p-channel thresholds increase from -0.9V to -1.3V, while the n-channel thresholds decrease from 1.05 to 0.23V, and the n-channel leakage remains below 1nA/mil. Excellent hardening results were also obtained on the polycode generator circuit. Ten circuits were irradiated to 1 x 10 6 rads (Si), and all continued to function well, with an increase in minimum power supply voltage from 2.85V to 5.85V and an increase in quiescent current by a factor of about 2. Similar hardening results were obtained on the 8-bit adder, with the minimum power supply voltage increasing from 2.2V to 4.6V and the add time increasing from 270 to 350 nsec after 1 x 10 6 rads (Si). These results show that large CMOS/SOS circuits can be hardened to above 1 x 10 6 rads (Si) with either the Si gate or Al gate technology. The paper also discusses the relative advantages of the Si gate versus the Al gate technology

Nash Equilibria in Symmetric Graph Games with Partial Observation

DEFF Research Database (Denmark)

Bouyer, Patricia; Markey, Nicolas; Vester, Steen

2017-01-01

We investigate a model for representing large multiplayer games, which satisfy strong symmetry properties. This model is made of multiple copies of an arena; each player plays in his own arena, and can partially observe what the other players do. Therefore, this game has partial information...... and symmetry constraints, which make the computation of Nash equilibria difficult. We show several undecidability results, and for bounded-memory strategies, we precisely characterize the complexity of computing pure Nash equilibria for qualitative objectives in this game model....

Generalizations of the Nash Equilibrium Theorem in the KKM Theory

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Sehie Park

2010-01-01

Full Text Available The partial KKM principle for an abstract convex space is an abstract form of the classical KKM theorem. In this paper, we derive generalized forms of the Ky Fan minimax inequality, the von Neumann-Sion minimax theorem, the von Neumann-Fan intersection theorem, the Fan-type analytic alternative, and the Nash equilibrium theorem for abstract convex spaces satisfying the partial KKM principle. These results are compared with previously known cases for G-convex spaces. Consequently, our results unify and generalize most of previously known particular cases of the same nature. Finally, we add some detailed historical remarks on related topics.

Experimental study of hypoxia-imaging agent 99mTc-HL91 in mice bearing glioblastoma G422

International Nuclear Information System (INIS)

Zhou Ying; Qu Wanying; Yao Zhiming; Chen Fang; Zhu Ming; Zhu Lin

1999-01-01

Objective: To evaluate the ability of detecting cerebral tumor by 99m Tc-HL91 in mice bearing glioblastoma G422. Methods: Six model mice underwent static whole body planar imagings at once and at 1,2,3,4,6,7,8 h postinjection of 99m Tc-HL91. Three mice each were killed at 4 h and 8 h, respectively. the tumor, blood and organs were removed, weighted and the radioactivity was measured. ROIs were drawn around tumor, head, contralateral axilla and chest in whole body planar images, and the radioactivity ratios of tumor to head (T/H), contralateral axilla (T/A) and chest (T/C) were calculated. Results: Increased tumor activity was identified in static whole body planar images since 1 h postinjection. At 2h postinjection, T/H, T/A and T/C were 2.93 +- 0.51, 4.86 +- 0.79 and 2.00 +- 0.35 respectively, which were significantly higher than those at once and at 1h postinjection (P 99m Tc-HL91 in tumor tissue of mice bearing glioblastoma G422 is increased and clearance rate is decreased. 99m Tc-HL91 imaging is suitable for glioblastoma at 2 h postinjection. It is appropriate to image tumors in head, neck, thorax, bone and soft tissues, but not in abdominal area

Differential requirements of two recA mutants for constitutive SOS expression in Escherichia coli K-12.

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Jarukit Edward Long

Full Text Available Repairing DNA damage begins with its detection and is often followed by elicitation of a cellular response. In E. coli, RecA polymerizes on ssDNA produced after DNA damage and induces the SOS Response. The RecA-DNA filament is an allosteric effector of LexA auto-proteolysis. LexA is the repressor of the SOS Response. Not all RecA-DNA filaments, however, lead to an SOS Response. Certain recA mutants express the SOS Response (recA(C in the absence of external DNA damage in log phase cells.Genetic analysis of two recA(C mutants was used to determine the mechanism of constitutive SOS (SOS(C expression in a population of log phase cells using fluorescence of single cells carrying an SOS reporter system (sulAp-gfp. SOS(C expression in recA4142 mutants was dependent on its initial level of transcription, recBCD, recFOR, recX, dinI, xthA and the type of medium in which the cells were grown. SOS(C expression in recA730 mutants was affected by none of the mutations or conditions tested above.It is concluded that not all recA(C alleles cause SOS(C expression by the same mechanism. It is hypothesized that RecA4142 is loaded on to a double-strand end of DNA and that the RecA filament is stabilized by the presence of DinI and destabilized by RecX. RecFOR regulate the activity of RecX to destabilize the RecA filament. RecA730 causes SOS(C expression by binding to ssDNA in a mechanism yet to be determined.

A freeze dried kit formulation for the preparation of {sup 99m} Tc labelled human polyclonal IgG for the detection of infection and inflammation; Desarrollo del nucleo equipo {sup 99m} Tc-IgG humana para la deteccion `In vivo` de procesos inflamatorios

Energy Technology Data Exchange (ETDEWEB)

Pedraza L, M

1996-11-01

A freeze dried kit formulation for the preparation of {sup 99m}Tc-labelled human polyclonal IgG for the detection of infection and inflammation employing direct methods for protein labeling was developed. The method comprises reduction of intrinsic disulphide bridges within the antibody molecule by the use of the reductant 2-mercaptoethanol. Following a subsequent purification, the resulting reduced antibody is labeled via Sn{sup 2+} reduction of pertechnetate in the presence of a weak competing ligand ethane-1-hydroxy-1,1-diphosphonate (EHDP). High labeling efficiencies (>90%) were obtained with high in vitro stability and without effect upon antibody immunoreactivity. Methods of analysis were also established permitting identification of radiochemical impurities which may be present in radiopharmaceutical solution. {sup 99m} Tc-polyclonal IgG prepared by the kit method was evaluated for scintigraphic localization of inflammatory lesions and abscesses in rabbits. Data demonstrated that the {sup 99m} Tc-polyclonal IgG after kit-reconstitution shows excellent stability and is an effective imaging agent of infection and/or inflammation. (Author).

Near-Nash equilibrium strategies for LQ differential games with inaccurate state information

Directory of Open Access Journals (Sweden)

2006-01-01

Full Text Available ε -Nash equilibrium or “near equilibrium” for a linear quadratic cost game is considered. Due to inaccurate state information, the standard solution for feedback Nash equilibrium cannot be applied. Instead, an estimation of the players' states is substituted into the optimal control strategies equation obtained for perfect state information. The magnitude of the ε in the ε -Nash equilibrium will depend on the quality of the estimation process. To illustrate this approach, a Luenberger-type observer is used in the numerical example to generate the players' state estimates in a two-player non-zero-sum LQ differential game.

Characterization of the SOS meta-regulon in the human gut microbiome.

Science.gov (United States)

Cornish, Joseph P; Sanchez-Alberola, Neus; O'Neill, Patrick K; O'Keefe, Ronald; Gheba, Jameel; Erill, Ivan

2014-05-01

Data from metagenomics projects remain largely untapped for the analysis of transcriptional regulatory networks. Here, we provide proof-of-concept that metagenomic data can be effectively leveraged to analyze regulatory networks by characterizing the SOS meta-regulon in the human gut microbiome. We combine well-established in silico and in vitro techniques to mine the human gut microbiome data and determine the relative composition of the SOS network in a natural setting. Our analysis highlights the importance of translesion synthesis as a primary function of the SOS response. We predict the association of this network with three novel protein clusters involved in cell wall biogenesis, chromosome partitioning and restriction modification, and we confirm binding of the SOS response transcriptional repressor to sites in the promoter of a cell wall biogenesis enzyme, a phage integrase and a death-on-curing protein. We discuss the implications of these findings and the potential for this approach for metagenome analysis.

Nash y von Neumann: mundos posibles y juegos de lenguaje

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Salazar , Boris

2004-06-01

Full Text Available Este ensayo emplea las nociones de juego de lenguaje y de equivalencia entre juegos para examinar la decisión de John Nash de no jugar el juego coalicional que propuso John von Neumann. El argumento central es que Nash concibió una clase de mundos posibles incompatible con la de von Neumann, y que en el origen de esa divergencia estarían sus distintas nociones de racionalidad.

CMOS/SOS 4k Rams hardened to 100 Krads (s:)

International Nuclear Information System (INIS)

Napoli, L.S.; Heagerty, W.F.; Smeltzer, R.K.; Yeh, J.L.

1982-01-01

Two CMOS/SOS 4K memories were fabricated with a recently developed, hardened SOS process. Memory functionality after radiation doses well in excess of 100 Krads(Si) was demonstrated. The critical device processing steps were identified. The radiationinduced failure mode of the memories is understood in terms of the circuit organization and the radiation behavior of the individual transistors in the memories

Radionuclides and inflammatory bowel diseases: 99mTc-sucralfate and 111 In-tropolonate-granulocytes

International Nuclear Information System (INIS)

Deveaux, M.; Macaigne, O.; Lecouffe, P.; Hossein-Foucher, CL.; Meuriot, S.; Venel, H.; Cortot, A.; Marchandise, X.

1989-01-01

111 In-tropolonate-granulocytes (G- 111 In) study was performed in 16 patients with inflammatory bowel disease (IBD). Images were obtained 3 h and 20 h post-injection. Counting of four days feacal excretion was more accurately expressed as daily intestinal granulocytes clearance. The day before, 12 of the patients had a sucralfate- 99m Tc scan (S- 99m Tc). Correlation between radioendoscopic data and S- 99m Tc scans was poor in 9 instances and there was no correlation between scan activity index and clinical and biological assessment. Correlation between G- 111 In scans and radioendoscopic data was excellent in 13 instances. Scan activity index was correlated with the Best index and with the intestinal alpha-1-antitrypsine clearance. Faecal excretion (range. 1 - 40%) and daily intestinal granulocytes clearance values (range. 03 - 50 milliards) were only correlated with protein loss parameters. So S- 99m Tc scan does not appear to be reliable, while intestinal G- 111 In clearance, not such easy to perform, can give an accurate assessment of IBD activity [fr

First evidence on the validity and reliability of the Safety Organizing Scale-Nursing Home version (SOS-NH).

Science.gov (United States)

Ausserhofer, Dietmar; Anderson, Ruth A; Colón-Emeric, Cathleen; Schwendimann, René

2013-08-01

The Safety Organizing Scale is a valid and reliable measure on safety behaviors and practices in hospitals. This study aimed to explore the psychometric properties of the Safety Organizing Scale-Nursing Home version (SOS-NH). In a cross-sectional analysis of staff survey data, we examined validity and reliability of the 9-item Safety SOS-NH using American Educational Research Association guidelines. This substudy of a larger trial used baseline survey data collected from staff members (n = 627) in a variety of work roles in 13 nursing homes (NHs) in North Carolina and Virginia. Psychometric evaluation of the SOS-NH revealed good response patterns with low average of missing values across all items (3.05%). Analyses of the SOS-NH's internal structure (eg, comparative fit indices = 0.929, standardized root mean square error of approximation = 0.045) and consistency (composite reliability = 0.94) suggested its 1-dimensionality. Significant between-facility variability, intraclass correlations, within-group agreement, and design effect confirmed appropriateness of the SOS-NH for measurement at the NH level, justifying data aggregation. The SOS-NH showed discriminate validity from one related concept: communication openness. Initial evidence regarding validity and reliability of the SOS-NH supports its utility in measuring safety behaviors and practices among a wide range of NH staff members, including those with low literacy. Further psychometric evaluation should focus on testing concurrent and criterion validity, using resident outcome measures (eg, patient fall rates). Copyright © 2013 American Medical Directors Association, Inc. All rights reserved.

Nash equilibrium in a pay-as-bid electricity market: Part 1- existence and characterization

Czech Academy of Sciences Publication Activity Database

Aussel, D.; Bendotti, P.; Pištěk, Miroslav

2017-01-01

Roč. 66, č. 6 (2017), s. 1013-1025 ISSN 0233-1934 R&D Projects: GA ČR GA15-00735S Institutional support: RVO:67985556 Keywords : Electricity market * multi-leader- follower game * Nash equilibrium * best response Subject RIV: AH - Economics OBOR OECD: Economic Theory Impact factor: 0.943, year: 2016 http://library.utia.cas.cz/separaty/2016/MTR/pistek-0468195.pdf

Sinusoidal obstruction syndrome (SOS): A light and electron microscopy study in human liver.

Science.gov (United States)

Vreuls, C P H; Driessen, A; Olde Damink, S W M; Koek, G H; Duimel, H; van den Broek, M A J; Dejong, C H C; Braet, F; Wisse, E

2016-05-01

Oxaliplatin is an important chemotherapeutic agent, used in the treatment of hepatic colorectal metastases, and known to induce the sinusoidal obstruction syndrome (SOS). Pathophysiological knowledge concerning SOS is based on a rat model. Therefore, the aim was to perform a comprehensive study of the features of human SOS, using both light microscopy (LM) and electron microscopy (EM). Included were all patients of whom wedge liver biopsies were collected during a partial hepatectomy for colorectal liver metastases, in a 4-year period. The wedge biopsy were perfusion fixated and processed for LM and EM. The SOS lesions were selected by LM and details were studied using EM. Material was available of 30 patients, of whom 28 patients received neo-adjuvant oxaliplatin. Eighteen (64%) of the 28 patients showed SOS lesions, based on microscopy. The lesions consisted of sinusoidal endothelial cell detachment from the space of Disse on EM. In the enlarged space of Disse a variable amount of erythrocytes were located. Sinusoidal endothelial cell detachment was present in human SOS, accompanied by enlargement of the space of Disse and erythrocytes in this area. These findings, originally described in a rat model, were now for the first time confirmed in human livers under clinically relevant settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

Overexpression of SOS genes in ciprofloxacin resistant Escherichia coli mutants.

Science.gov (United States)

Pourahmad Jaktaji, Razieh; Pasand, Shirin

2016-01-15

Fluoroquinolones are important antibiotics for the treatment of urinary tract infections caused by Escherichia coli. Mutational studies have shown that ciprofloxacin, a member of fluoroquinolones induces SOS response and mutagenesis in pathogenic bacteria which in turn develop antibiotic resistance. However, inhibition of SOS response can increase recombination activity which in turn leads to genetic variation. The aim of this study was to measure 5 SOS genes expressions in nine E. coli mutants with different MICs for ciprofloxacin following exposure to ciprofloxacin. Gene expression was assessed by quantitative real time PCR. Gene alteration assessment was conducted by PCR amplification and DNA sequencing. Results showed that the expression of recA was increased in 5 mutants. This overexpression is not related to gene alteration, and enhances the expression of polB and umuCD genes encoding nonmutagenic and mutagenic polymerases, respectively. The direct relationship between the level of SOS expression and the level of resistance to ciprofloxacin was also indicated. It was concluded that novel therapeutic strategy that inhibits RecA activity would enhance the efficiency of common antibiotics against pathogenic bacteria. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of dietary supplementation with betaine on a nonalcoholic steatohepatitis (NASH) mouse model.

Science.gov (United States)

Kawakami, Sakura; Han, Kyu-Ho; Nakamura, Yumi; Shimada, Ken-ichiro; Kitano, Tomoko; Aritsuka, Tsutomu; Nagura, Taizo; Ohba, Kiyoshi; Nakamura, Kimihide; Fukushima, Michihiro

2012-01-01

The effects of betaine supplementation on non-alcoholic steatohepatitis (NASH) model mice were examined by measuring the accumulation of fat in the livers of NASH model mice compared to a control. Betaine from sugar beets was provided to the model mice as a dietary supplement. After 3 wk of dietary supplementation, there were no significant differences in body weight or liver weight between the groups. However, the liver to body weight ratio in the high-fat diet with betaine (HFB) group was significantly (pNASH model mice.

Detection of experimental infections with 99mTc-labeled monoclonal antibodies against TNF-α and interleukin-8

International Nuclear Information System (INIS)

Welling, Mick; Feitsma, Hans I.J.; Calame, Wim; Pauwels, Ernest K.J.

1997-01-01

This study was designed to assess monoclonal antibodies (MAbs) directed against tumor necrosis factor-α (TNF-α) (anti-TNF) or interleukin-8 (anti-IL-8) as radioactive agents for the detection of Staphylococcus aureus- or Klebsiella pneumoniae-infected thighs in mice. At 5 min (acute infection) or 20 h (established) post-infection, 20 μg of the 99m Tc-labeled MAbs were injected. At various time intervals, the accumulation of the radiotracer in the infected thighs was assessed and expressed as a target-to-nontarget (T/NT) ratio. The binding of 99m Tc-labeled MAbs to circulating mononuclear cells and granulocytes was quantitated 20 h after injection. The pharmacokinetics of the MAbs, in relation to the control agents 99m Tc-labeled polyclonal human immunoglobulin (IgG) and a 99m Tc-labeled nonspecific IgG1 MAb, were also studied. In acute infections, 99m Tc-anti-TNF accumulated to a higher extent (p 99m Tc-IgG and was higher at 0.25 h in K. pneumoniae-infected mice (p 99m Tc-IgG. In established S. aureus and K. pneumoniae infections, 99m Tc-anti-IL-8 detected the infection more intensely than 99m Tc-IgG until 1 h after injection. In both S. aureus and K. pneumoniae infections, localization of sites of infection correlates (p 99m Tc-labeled MAbs to granulocytes and mononuclear cells in both acute and established infections. It was concluded that 99m Tc-labeled MAbs, directed against TNF-α and IL-8, accumulate in bacterial infections in mice to a higher extent than does 99m Tc-IgG after infection and is related to the binding of the antibodies to blood leukocytes. With these 99m Tc-labeled MAbs, information might be gained about the development of an infection

Activation of Extracellular Signal-Regulated Kinase but Not of p38 Mitogen-Activated Protein Kinase Pathways in Lymphocytes Requires Allosteric Activation of SOS

Science.gov (United States)

Jun, Jesse E.; Yang, Ming; Chen, Hang; Chakraborty, Arup K.

2013-01-01

Thymocytes convert graded T cell receptor (TCR) signals into positive selection or deletion, and activation of extracellular signal-related kinase (ERK), p38, and Jun N-terminal protein kinase (JNK) mitogen-activated protein kinases (MAPKs) has been postulated to play a discriminatory role. Two families of Ras guanine nucleotide exchange factors (RasGEFs), SOS and RasGRP, activate Ras and the downstream RAF-MEK-ERK pathway. The pathways leading to lymphocyte p38 and JNK activation are less well defined. We previously described how RasGRP alone induces analog Ras-ERK activation while SOS and RasGRP cooperate to establish bimodal ERK activation. Here we employed computational modeling and biochemical experiments with model cell lines and thymocytes to show that TCR-induced ERK activation grows exponentially in thymocytes and that a W729E allosteric pocket mutant, SOS1, can only reconstitute analog ERK signaling. In agreement with RasGRP allosterically priming SOS, exponential ERK activation is severely decreased by pharmacological or genetic perturbation of the phospholipase Cγ (PLCγ)-diacylglycerol-RasGRP1 pathway. In contrast, p38 activation is not sharply thresholded and requires high-level TCR signal input. Rac and p38 activation depends on SOS1 expression but not allosteric activation. Based on computational predictions and experiments exploring whether SOS functions as a RacGEF or adaptor in Rac-p38 activation, we established that the presence of SOS1, but not its enzymatic activity, is critical for p38 activation. PMID:23589333

Influence of the gene xthA in the activation of SOS response of Escherichia coli; Influencia del gen xthA en la activacion de la respuesta SOS de Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Dominguez M, V.

2013-07-01

The SOS response is one of the strategies that has Escherichia coli to counteract the lesions in the genetic material. The response is integrated for approximately 60 genes that when are activated they provide to the cell a bigger opportunity to survive. For the activation of this system is necessary that DNA regions of simple chain are generated, in such a way that most of the lesions should be processed, to be able to induce this answer. Some genes that intervene in this procedure, as recO, recB and recJ are recognized since when being exposed to the radiation, their activity SOS is smaller than in a wild strain. In previous works has been studied that to inactivate the genes that are involves in the lesions processing to generate DNA of simple chain, the SOS induction level diminishes with regard to a wild strain, but that when eliminating the genes that are involves directly in the repair, the SOS response increases. In this work a strain with defects in the gene xthA was built, which encodes for an endonuclease AP that participates in the repair mechanism by base excision and was evaluated their sensibility as the activity of the SOS response when exposing it to UV light and gamma radiation. The results showed that the lethality of the strain with the defect is very similar to the wild strain; while the activation level of the SOS response is bigger in comparison with the wild strain when being exposed to UV light; suggesting the existence of an enzyme that recognizes the lesions that produces this radiation, however, is not this the main repair channel, since the survival is similar to that of the wild strain. On the contrary, the results obtained with gamma radiation showed that the lethality diminishes in comparison to that of the wild strain, like the SOS activity; due surely to that the gene product intervenes in the repair for base excision, participating in the formation of the previous substrate to the activation of the SOS response. (Author)

Switching of the positive feedback for RAS activation by a concerted function of SOS membrane association domains.

Science.gov (United States)

Nakamura, Yuki; Hibino, Kayo; Yanagida, Toshio; Sako, Yasushi

2016-01-01

Son of sevenless (SOS) is a guanine nucleotide exchange factor that regulates cell behavior by activating the small GTPase RAS. Recent in vitro studies have suggested that an interaction between SOS and the GTP-bound active form of RAS generates a positive feedback loop that propagates RAS activation. However, it remains unclear how the multiple domains of SOS contribute to the regulation of the feedback loop in living cells. Here, we observed single molecules of SOS in living cells to analyze the kinetics and dynamics of SOS behavior. The results indicate that the histone fold and Grb2-binding domains of SOS concertedly produce an intermediate state of SOS on the cell surface. The fraction of the intermediated state was reduced in positive feedback mutants, suggesting that the feedback loop functions during the intermediate state. Translocation of RAF, recognizing the active form of RAS, to the cell surface was almost abolished in the positive feedback mutants. Thus, the concerted functions of multiple membrane-associating domains of SOS governed the positive feedback loop, which is crucial for cell fate decision regulated by RAS.

SoS Notebook: An Interactive Multi-Language Data Analysis Environment.

Science.gov (United States)

Peng, Bo; Wang, Gao; Ma, Jun; Leong, Man Chong; Wakefield, Chris; Melott, James; Chiu, Yulun; Du, Di; Weinstein, John N

2018-05-22

Complex bioinformatic data analysis workflows involving multiple scripts in different languages can be difficult to consolidate, share, and reproduce. An environment that streamlines the entire processes of data collection, analysis, visualization and reporting of such multi-language analyses is currently lacking. We developed Script of Scripts (SoS) Notebook, a web-based notebook environment that allows the use of multiple scripting language in a single notebook, with data flowing freely within and across languages. SoS Notebook enables researchers to perform sophisticated bioinformatic analysis using the most suitable tools for different parts of the workflow, without the limitations of a particular language or complications of cross-language communications. SoS Notebook is hosted at http://vatlab.github.io/SoS/ and is distributed under a BSD license. bpeng@mdanderson.org.

Effects of N-3 Fish Oil on Metabolic and Histological Parameters in NASH: A Double-Blind, Randomized, Placebo-Controlled Trial

Science.gov (United States)

Argo, Curtis K.; Patrie, James T.; Lackner, Carolin; Henry, Thomas D.; deLange, Eduard E.; Weltman, Arthur L.; Shah, Neeral L.; Al-Osaimi, Abdullah M.; Pramoonjago, Patcharin; Jayakumar, Saumya; Binder, Lukas P.; Simmons-Egolf, Winsor D.; Burks, Sandra G.; Bao, Yongde; Taylor, Anne Gill; Rodriguez, Jessica; Caldwell, Stephen H.

2014-01-01

This study’s aim was to assess the histological and metabolic effects of N-3 polyunsaturated fatty acids (PUFA) versus placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). Methods Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received N-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counseling on caloric intake and physical activity for all subjects. Results N-3- and placebo-treated groups showed no significant difference for the primary endpoint of NAS reduction ≥ 2 points without fibrosis progression after adjustment for known covariates (N-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p=0.99). Among subjects with increased or stable weight, N-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p=0.014 for 2nd quartile, p=0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. Conclusion N-3 PUFA at 3000 mg/day for one year did not lead to improvement in the primary outcome of histological activity in NASH patients (≥ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of N-3 therapy would lead to additional benefit is uncertain. PMID:25195547

Effect of radiation doses rate on SOS response induction in irradiated Escherichia coli Cells

International Nuclear Information System (INIS)

Cuetara Lugo, Elizabeth B.; Fuentes Lorenzo, Jorge L.; Almeida Varela, Eliseo; Prieto Miranda, Enrique F.; Sanchez Lamar, Angel; Llagostera Casal, Montserrat

2005-01-01

The present work is aimed to study the effect of radiation dose rate on the induction of SOS response in Escherichia coli cells. We measured the induction of sul A reporter gene in PQ-37 (SOS Chromotest) cells. Lead devises were built with different diameter and these were used for diminishing the dose rate of PX- -30M irradiator. Our results show that radiation doses rate significantly modifies the induction of SOS response. Induction factor increases proportionally to doses rate in Escherichia coli cells defective to nucleotide excision repair (uvrA), but not in wild type cells. We conclude that the dose rate affects the level of induction of SOS response

The Arabidopsis thaliana mutant air1 implicates SOS3 in the regulation of anthocyanins under salt stress

KAUST Repository

Van Oosten, Michael James

2013-08-08

The accumulation of anthocyanins in plants exposed to salt stress has been largely documented. However, the functional link and regulatory components underlying the biosynthesis of these molecules during exposure to stress are largely unknown. In a screen of second site suppressors of the salt overly sensitive3-1 (sos3-1) mutant, we isolated the anthocyanin-impaired-response-1 (air1) mutant. air1 is unable to accumulate anthocyanins under salt stress, a key phenotype of sos3-1 under high NaCl levels (120 mM). The air1 mutant showed a defect in anthocyanin production in response to salt stress but not to other stresses such as high light, low phosphorous, high temperature or drought stress. This specificity indicated that air1 mutation did not affect anthocyanin biosynthesis but rather its regulation in response to salt stress. Analysis of this mutant revealed a T-DNA insertion at the first exon of an Arabidopsis thaliana gene encoding for a basic region-leucine zipper transcription factor. air1 mutants displayed higher survival rates compared to wild-type in oxidative stress conditions, and presented an altered expression of anthocyanin biosynthetic genes such as F3H, F3′H and LDOX in salt stress conditions. The results presented here indicate that AIR1 is involved in the regulation of various steps of the flavonoid and anthocyanin accumulation pathways and is itself regulated by the salt-stress response signalling machinery. The discovery and characterization of AIR1 opens avenues to dissect the connections between abiotic stress and accumulation of antioxidants in the form of flavonoids and anthocyanins. © 2013 Springer Science+Business Media Dordrecht.

Phosphine reduced IgG. A new method for {sup 99m}Tc labeling immunoglobulins

Energy Technology Data Exchange (ETDEWEB)

Arteaga de Murphy, C; Melendez-Alafort, L [Radiofarmacia Departamento de Medicina Nuclear, Instituto Nacional de Nutricion Salvador Zubiran, Mexico (Mexico); Martinez-Rivero, O [Laboratorio de Quimica Organica, Facultad de Quimica, Universidad de la Habana, Habana (Cuba); Gomez, E [Departamento de Fisiologia de la Nutricion, Instituto Nacional de Nutricion Salvador Zubiran, Mexico (Mexico); Ferro-Flores, G [Depeartamento del Reactor y Materiales Radioactivos, Instituto Nacional de Investigaciones Nucleares, Mexico (Mexico)

1997-09-01

A new technetium labeling method for immunoglobulins reduced with tris(2-carboxy-ethyl)phosphine hydrochloride is presented. The Sandoglobulina IgG source was assayed for purity and optimum reagent`s concentration and incubation times were determined. It was purified by column chromatography and labelled with Sn{sup 2+} reduced technetium in the presence of MDP. The kit is easy to prepare, labeling efficiency is >(97{+-}1.9)% and stable for 6 hours.The immunoreactivity of the {sup 99}Tc-IgG was verified by electrophoresis and Western blot tests. The IgG retained its structure after both the reducing and labeling processes and it was the only labeled species. (author). 11 refs.

Water extract of Vitis coignetiae Pulliat leaves attenuates oxidative stress and inflammation in progressive NASH rats.

Science.gov (United States)

Pak, Wing; Takayama, Fusako; Hasegawa, Azusa; Mankura, Mitsumasa; Egashira, Toru; Ueki, Keiji; Nakamoto, Kazuo; Kawasaki, Hiromu; Mori, Akitane

2012-01-01

This study aimed to investigate the therapeutic effects of the water extract of leaves of Vitis coignetiae Pulliat (VCPL) on nonalcoholic steatohepatitis (NASH) with advanced fibrosis, as our previous study exhibited its preventive effect on NASH. The NASH animal model [PCT/JP2007/52477] was prepared by loading recurrent and intermittent hypoxemia stress to a rat with fatty liver, which resembled the condition occurring in patients with obstructive sleep apnea (OSA) and fatty liver, who have a high incidence of NASH. Intermittent hypoxemia stress is regarded as a condition similar to warm ischemia followed by re-oxygenation, which induces oxidative stress (OS). The daily 100 or 300 mg/kg VCPL administrations were performed for 3 weeks perorally beginning at the time of detection of advanced liver fibrosis. The therapeutic efficacy of VCPL on NASH was demonstrated by the reduction of the leakage of hepato-biliary enzymes and the amelioration of liver fibrosis. The OS elevation in NASH rats was measured based on the derivation of reactive oxygen species from liver mitochondrial energy metabolism and on the decrease in plasma SOD-like activity. The aggravation of inflammatory responses was demonstrated by the neutrophil infiltration (elevated myeloperoxidase activity) and the progression of fibrosis in the livers of NASH rats. In addition, the NASH rats without VCPL treatment also exhibited activation of nuclear factor-κB, a key factor in the link between oxidative stress and inflammation. All of these changes were reduced dose-dependently by the VCPL administration. These findings indicate that VCPL may improve hepatic fibrosis or at least suppress the progression of NASH, by breaking the crosstalk between OS and inflammation.

Alleviation of insulin resistance and liver damage by oral administration of Imm124-E is mediated by increased Tregs and associated with increased serum GLP-1 and adiponectin: results of a phase I/II clinical trial in NASH

Directory of Open Access Journals (Sweden)

Mizrahi M

2012-12-01

Full Text Available Meir Mizrahi,1 Yehudit Shabat,1 Ami Ben Ya'acov,1 Gadi Lalazar,1 Tomer Adar,1 Victor Wong,2 Brian Muller,2 Grant Rawlin,2 Yaron Ilan11Liver Unit, Hebrew University-Hadassah Medical Center, Jerusalem, Israel; 2Immuron Limited, North Melbourne, AustraliaBackground: Nonalcoholic steatohepatitis (NASH is considered to be part of the nonalcoholic fatty liver disorders and its incidence is increasing. Imm124-E (Immuron Ltd, Melbourne, Australia, containing hyperimmune bovine colostrum, has been shown to exert an immunomodulatory effect and to alleviate target organ damage in animal models of NASH. The aim of our study was to determine the safety and efficacy of oral administration of Imm124-E to patients with insulin resistance and NASH.Methods: In an open-label trial, ten patients with biopsy-proven NASH and insulin resistance were orally treated with Imm124-E for 30 days.Results: Oral administration of Imm124-E was safe, and no side effects were noted. Alleviation of insulin resistance was reflected by significantly improved hemoglobin A1c (HbA1c values in all ten treated patients. For between five and eight responders, the following effects were noted: a decrease in fasting glucose levels; improved oral glucose tolerance test (OGGT and homeostatic model assessment insulin resistance (HOMA scores; and alleviation in lipid profile. These effects were accompanied by increased serum levels of glucagon-like peptide 1 (GLP-1, adiponectin and T regulatory cells.Conclusion: Hyperimmune colostrum alleviates NASH.Keywords: NASH, anti-LPS, diabetes, adipokines, regulatory T cells

34 CFR 99.21 - Under what conditions does a parent or eligible student have the right to a hearing?

Science.gov (United States)

2010-07-01

... have the right to a hearing? 99.21 Section 99.21 Education Office of the Secretary, Department of Education FAMILY EDUCATIONAL RIGHTS AND PRIVACY What Are the Procedures for Amending Education Records? § 99.21 Under what conditions does a parent or eligible student have the right to a hearing? (a) An...

Synthesis of insulin-like growth factor 1 analogue (188Re/99Tcm-IGF-1A) and the binding with pancreatic carcinoma cell

International Nuclear Information System (INIS)

Zhang Bin; Wu Yiwei; Fan Guanglei; Fan Wo

2007-01-01

Objective: An useful and stable method was developed for labeling insulin-like growth factor 1 analogue (IGF-1A) with 188 Re/ 99 Tc m , and its binding characteristic was studied with human pancreatic cancer cell Patu8988 in this study. Methods: The direct labeling method was adopted to label IGF- 1A under different conditions: 2 to 10 μl Tween80; 0.75 to 25 g/L SnCl 2 ·2H 2 O; 20 to 100 μg IGF-1A; 10 to 500 μl 188 ReO 4 - . The labeling rate was dynamically measured from 5 min to 6 h after labeling. The in vitro stabilities of 188 Re/ 99 Tc m -IGF-1A were accessed by dynamic labeling rates measured at 2 to 24 h. SPECT imaging after intravenous injection of 99 Tc m -IGF-1A and intratumoral injection of 188 Re-IGF-1A in nude mice was performed. Results: The best condition for labeling 188 Re was: 100 μl SnCl 2 ·2H 2 O (10 g/L), 50 μl IGF-1A (2 g/L), 300 μl Na 3 PO 4 , l0 μl 0.1% Tween80, 50 μl 188 ReO 4 - with 30 min reaction time at room temperature and pH 7.0. The maximum labeling rate of 188 Re-IGF-1A was (94.07 ± 0.32)%. The radiochemical purity was (76.57 ± 9.96)% at 24 h after mixing with human serum. The maximum binding efficiency of 188 Re-IGF-1A with Patu8988 cell was (24.13 ± 2.03)% , and the specific binding was 12.68%. The best labeling condition of 99 Tc m was: 100 μl SnCl 2 ·2H 2 O (3 g/L), 40 μl IGF-1A (2 g/L), 2 μl 0.1% Tween80, 50 μl 99 Tc m O - 4. The maximum labeling rate of 99 Tc m -IGF-1A was (94.43 ± 0.75)% and the radiochemical purity was (54.07 ± 3.86)% at 24 h after mixing with human serum. The maximum binding with Patu8988 cell was (22.95 ± 3.94)%, and the specific binding rate was 19.31%. The tumors in nude mice could be best imaged at 6 h after intravenous injection of 99 Tc m -IGF-1A and 48 h after intratumoral injection of 188 Re-IGF-1A. Conclusions: The presented method of labeling IGF-1A with 188 Re/ 99 Tc m was stable and efficient. 188 Re/ 99 Tc m -IGF-1A could bind with the pancreatic cancer cell Patu8988

Progression and Regression of Hepatic Lesions in a Mouse Model of NASH Induced by Dietary Intervention and Its Implications in Pharmacotherapy

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Zhi-Ming Ding

2018-05-01

Full Text Available Understanding of the temporal changes of hepatic lesions in the progression and regression of non-alcoholic steatohepatitis (NASH is vital to elucidation of the pathogenesis of NASH, and critical to the development of a strategy for NASH pharmacotherapy. There are challenges in studying hepatic lesion progression and regression in NASH patients due to the slow development of NASH in humans, one being the requirement for multiple biopsies during the longitudinal follow-up. Here we studied lesion progression and regression in the diet-induced animal model of NASH by application or removal of the pathogenic diet for multiple time periods. Male C57BL/6 mice fed Western diet developed progressive hepatic steatosis/macrovesicular vacuolation, inflammation, and hepatocyte degeneration, as well as perisinusoidal fibrosis and occasionally portal fibrosis as early as 2 months after initiation of the Western diet. In the same period, the mice exhibited elevated ALT (alanine aminotransferase and AST (aspartate aminotransferase enzyme activities, CK18 (cytokeratin−18, PIIINP (N-terminal propeptide of type III collagen, and TIMP-1 (tissue inhibitor of metalloproteinase−1. Hepatic steatosis diminished rapidly when the Western diet was replaced by normal rodent chow diet and hepatic inflammation and hepatocyte degeneration were also reduced. Interestingly, perisinusoidal fibrosis and portal fibrosis regressed 8 months after chow diet replacement. To understand pharmacotherapy for NASH, mice with established NASH hepatic lesions were treated with either FXR agonist obeticholic acid (Ocaliva, or CCR2/5 antagonist Cenicriviroc. Similar to the diet replacement, metabolic modulator Ocaliva markedly reduced steatosis/macrovesicular vacuolation, hepatic inflammation, and hepatocyte degeneration effectively, but exhibited no significant effect on liver fibrosis. Anti-inflammation drug Cenicriviroc, on the other hand, markedly decreased inflammation and hepatocyte

A syntactic commutativity format for SOS

NARCIS (Netherlands)

Mousavi, M.R.; Reniers, M.A.; Groote, J.F.

2005-01-01

Considering operators defined using Structural Operational Semantics (SOS), commutativity axioms are intuitive properties that hold for many of them. Proving this intuition is usually a laborious task, requiring several pages of boring and standard proof. To save this effort, we propose a syntactic

Motion-insensitive carotid intraplaque hemorrhage imaging using 3D inversion recovery preparation stack of stars (IR-prep SOS) technique.

Science.gov (United States)

Kim, Seong-Eun; Roberts, John A; Eisenmenger, Laura B; Aldred, Booth W; Jamil, Osama; Bolster, Bradley D; Bi, Xiaoming; Parker, Dennis L; Treiman, Gerald S; McNally, J Scott

2017-02-01

Carotid artery imaging is important in the clinical management of patients at risk for stroke. Carotid intraplaque hemorrhage (IPH) presents an important diagnostic challenge. 3D magnetization prepared rapid acquisition gradient echo (MPRAGE) has been shown to accurately image carotid IPH; however, this sequence can be limited due to motion- and flow-related artifact. The purpose of this work was to develop and evaluate an improved 3D carotid MPRAGE sequence for IPH detection. We hypothesized that a radial-based k-space trajectory sequence such as "Stack of Stars" (SOS) incorporated with inversion recovery preparation would offer reduced motion sensitivity and more robust flow suppression by oversampling of central k-space. A total of 31 patients with carotid disease (62 carotid arteries) were imaged at 3T magnetic resonance imaging (MRI) with 3D IR-prep Cartesian and SOS sequences. Image quality was determined between SOS and Cartesian MPRAGE in 62 carotid arteries using t-tests and multivariable linear regression. Kappa analysis was used to determine interrater reliability. In all, 25 among 62 carotid plaques had carotid IPH by consensus from the reviewers on SOS compared to 24 on Cartesian sequence. Image quality was significantly higher with SOS compared to Cartesian (mean 3.74 vs. 3.11, P SOS acquisition yielded sharper image features with less motion (19.4% vs. 45.2%, P SOS (kappa = 0.89), higher than that of Cartesian (kappa = 0.84). By minimizing flow and motion artifacts and retaining high interrater reliability, the SOS MPRAGE has important advantages over Cartesian MPRAGE in carotid IPH detection. 1 J. Magn. Reson. Imaging 2017;45:410-417. © 2016 International Society for Magnetic Resonance in Medicine.

How hard is it to find extreme Nash equilibria in network congestion games?

NARCIS (Netherlands)

Gassner, E.; Hatzl, J.; Krumke, S.O.; Sperber, H.; Woeginger, G.J.; Papadimitriou, C.; Zhang, S.

2008-01-01

We study the complexity of finding extreme pure Nash equilibria in symmetric (unweighted) network congestion games. In our context best and worst equilibria are those with minimum respectively maximum makespan. On series-parallel graphs a worst Nash equilibrium can be found by a Greedy approach

P G Babu

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education. P G Babu. Articles written in Resonance – Journal of Science Education. Volume 3 Issue 7 July 1998 pp 53-60 General Article. Game Theory - Nash Equilibrium · P G Babu · More Details Fulltext PDF. Volume 3 Issue 8 August 1998 pp 46-55 General Article.

Evolving Concepts in the Pathogenesis of NASH: Beyond Steatosis and Inflammation

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William Peverill

2014-05-01

Full Text Available Non-alcoholic steatohepatitis (NASH is characterised by hepatic steatosis and inflammation and, in some patients, progressive fibrosis leading to cirrhosis. An understanding of the pathogenesis of NASH is still evolving but current evidence suggests multiple metabolic factors critically disrupt homeostasis and induce an inflammatory cascade and ensuing fibrosis. The mechanisms underlying these changes and the complex inter-cellular interactions that mediate fibrogenesis are yet to be fully elucidated. Lipotoxicity, in the setting of excess free fatty acids, obesity, and insulin resistance, appears to be the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence contribute to activation of the inflammasome via a variety of intra- and inter-cellular signalling mechanisms leading to fibrosis. Current evidence suggests that periportal components, including the ductular reaction and expansion of the hepatic progenitor cell compartment, may be involved and that the Th17 response may mediate disease progression. This review aims to provide an overview of the pathogenesis of NASH and summarises the evidence pertaining to key mechanisms implicated in the transition from steatosis and inflammation to fibrosis. Currently there are limited treatments for NASH although an increasing understanding of its pathogenesis will likely improve the development and use of interventions in the future.

SOS hotline for women victims of discrimination at the workplace

OpenAIRE

Dobrosavljević-Grujić Ljiljana S.

2004-01-01

SOS hotline for women victims of discrimination at the workplace offers free legal assistance to women, whenever their labor rights are endangered. If the dispute cannot be resolved peacefully by mediation between employer and employees, female lawyer skilled for the labor law starts up judicial proceedings. Some characteristic cases of discrimination of women from the practice of SOS telephone, such as dismissal from the work, physical violence and sexual blackmail, are presented in the paper.

Preparation of hypoxic imaging agents 99Tcm-MNLS and 99Tcm-MLS and their biodistribution in mice

International Nuclear Information System (INIS)

Zha Zhihao; Wang Jianjun; Zhu Lin

2009-01-01

To develop 99 Tc m labeled hypoxic agents,two phosphate-based chelating agents were coupled to metronidazole, 2- (2-methyl-5-nitro-1H-imidazol-1-yl) ethyl dihydrogen phosphate (MNLS) and its analog 2- (2-methyl-1H-imidazol-1-yl) ethyl dihydrogen phosphate (MLS) were synthesized based on the mechanism of prodrug. Labeling yield of these 99 Tc m complexes were more than 90% as proved by TLC. Paper electrophoresis showed that these complexes were neutral. Biodistribution of these complexes in tumor-bearing mice showed that the uptake of 99 Tc m -MNLS (120 min, 2.99 ± 0.25 ID%/g) in tumor was higher than that of 99 Tc m -HL91 (120 min, 0.93 ± 0.13 ID%/g) and 99 Tc m -MLS (120 min, 1.61 ± 0.13 ID%/g), and the uptake ratio of tumor to muscle and tumor to liver of 99 Tc m -MNLS (120 min, 5.90, 1.03) were higher than that of 99 Tc m -HL91 (120 min, 3.59, 0.17) and 99 Tc m -MLS (120 min, 5.40, 0.13). The higher tumor uptake for 99 Tc m -MNLS than 99 Tc m -MLS suggested that nitroimidazole was a key group for tumor accumulation. 99 Tc m -MNLS had higher tumor uptake and lower liver uptake, which had the potential for tumor imaging and was worth of further vestigation. (authors)

Design rules for RCA self-aligned silicon-gate CMOS/SOS process

Science.gov (United States)

1977-01-01

The CMOS/SOS design rules prepared by the RCA Solid State Technology Center (SSTC) are described. These rules specify the spacing and width requirements for each of the six design levels, the seventh level being used to define openings in the passivation level. An associated report, entitled Silicon-Gate CMOS/SOS Processing, provides further insight into the usage of these rules.

Altered cellular redox status, sirtuin abundance and clock gene expression in a mouse model of developmentally primed NASH.

Science.gov (United States)

Bruce, Kimberley D; Szczepankiewicz, Dawid; Sihota, Kiran K; Ravindraanandan, Manoj; Thomas, Hugh; Lillycrop, Karen A; Burdge, Graham C; Hanson, Mark A; Byrne, Christopher D; Cagampang, Felino R

2016-07-01

We have previously shown that high fat (HF) feeding during pregnancy primes the development of non-alcoholic steatohepatits (NASH) in the adult offspring. However, the underlying mechanisms are unclear. Since the endogenous molecular clock can regulate hepatic lipid metabolism, we investigated whether exposure to a HF diet during development could alter hepatic clock gene expression and contribute to NASH onset in later life. Female mice were fed either a control (C, 7%kcal fat) or HF (45%kcal fat) diet. Offspring were fed either a C or HF diet resulting in four offspring groups: C/C, C/HF, HF/C and HF/HF. NAFLD progression, cellular redox status, sirtuin expression (Sirt1, Sirt3), and the expression of core clock genes (Clock, Bmal1, Per2, Cry2) and clock-controlled genes involved in lipid metabolism (Rev-Erbα, Rev-Erbβ, RORα, and Srebp1c) were measured in offspring livers. Offspring fed a HF diet developed NAFLD. However HF fed offspring of mothers fed a HF diet developed NASH, coupled with significantly reduced NAD(+)/NADH (pNASH in adulthood, involving altered cellular redox status, reduced sirtuin abundance, and desynchronized clock gene expression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Serum Oxidative Stress Markers and Lipidomic Profile to Detect NASH Patients Responsive to an Antioxidant Treatment: A Pilot Study

Directory of Open Access Journals (Sweden)

Paola Stiuso

2014-01-01

Full Text Available Liver steatosis can evolve to steatohepatitis (NASH through a series of biochemical steps related to oxidative stress in hepatocytes. Antioxidants, such as silybin, have been proposed as a treatment of patients with nonalcoholic fatty liver disease (NAFLD and NASH. In this study, we evaluated, in patients with histologically documented NASH, the oxidant/antioxidant status and lipid “fingerprint” in the serum of NASH patients, both in basal conditions and after 12 months of treatment with silybin-based food integrator Realsil (RA. The oxidant/antioxidant status analysis showed the presence of a group of patients with higher basal severity of disease (NAS scores 4.67 ± 2.5 and a second group corresponding to borderline NASH (NAS scores = 3.8 ± 1.5. The chronic treatment with RA changed the NAS score in both groups that reached the statistical significance only in group 2, in which there was also a significant decrease of serum lipid peroxidation. The lipidomic profile showed a lipid composition similar to that of healthy subjects with a restoration of the values of free cholesterol, lysoPC, SM, and PC only in group 2 of patients after treatment with RA. Conclusion. These data suggest that lipidomic and/or oxidative status of serum from patients with NASH could be useful as prognostic markers of response to an antioxidant treatment.

99mTcO(MAG2-3G3-dimer): a new integrin αvβ3-targeted SPECT radiotracer with high tumor uptake and favorable pharmacokinetics

International Nuclear Information System (INIS)

Shi, Jiyun; Wang, Lijun; Kim, Young-Seung; Zhai, Shizhen; Liu, Shuang; Jia, Bing; Wang, Fan

2009-01-01

This report presents the synthesis of a cyclic RGD dimer conjugate, MAG 2 -G 3 -E[G 3 -c(RGDfK)] 2 (MAG 2 -3G 3 -dimer, G 3 = Gly-Gly-Gly, MAG 2 = S-benzoyl mercaptoacetylglycylglycyl), and evaluation of its 99m Tc complex, 99m TcO(MAG 2 -3G 3 -dimer), as a new radiotracer for imaging the tumor integrin α v β 3 expression. An in vitro displacement assay was used to determine the integrin α v β 3 binding affinity of MAG 2 -3G 3 -dimer against 125 I-c(RGDyK) bound to U87MG human glioma cells. The athymic nude mice bearing U87MG glioma xenografts were used for biodistribution and planar imaging studies. We found that (1) MAG 2 is such a highly effective bifunctional chelator that 99m TcO(MAG 2 -3G 3 -dimer) can be prepared in high yield (radiochemical purity >95%) and with high specific activity (∝5 Ci/μmol) using a kit formulation; (2) 99m TcO(MAG 2 -3G 3 -dimer) has very high solution stability in the kit matrix; and (3) 99m TcO(MAG 2 -3G 3 -dimer) has very fast clearance kinetics from the intestine, liver, and kidneys. Among the 99m Tc-labeled cyclic RGD peptides evaluated in the xenografted U87MG glioma models, 99m TcO(MAG 2 -3G 3 -dimer) has the best pharmacokinetics and tumor to background ratios (tumor/liver = 4.29 ± 1.00 at 30 min postinjection and 8.29 ± 1.50 at 120 min postinjection; tumor/kidney = 1.16 ± 0.19 at 30 min postinjection and 2.49 ± 0.25 at 120 min postinjection). Planar imaging studies showed that tumors in the glioma-bearing mice administered with 99m TcO(MAG 2 -3G 3 -dimer) can be visualized with excellent contrast as early as 15 min postinjection. 99m TcO(MAG 2 -3G 3 -dimer) was able to maintain its chemical integrity in kidneys (>80% intact) and liver (>95% intact) over the 2-h period. However, there was significant metabolism (>50% of the injected radioactivity) detected in both urine and feces samples. 99m TcO(MAG 2 -3G 3 -dimer) is a very attractive radiotracer for early detection of integrin α v β 3 -positive tumors and has

SOS hotline for women victims of discrimination at the workplace

Directory of Open Access Journals (Sweden)

Dobrosavljević-Grujić Ljiljana S.

2004-01-01

Full Text Available SOS hotline for women victims of discrimination at the workplace offers free legal assistance to women, whenever their labor rights are endangered. If the dispute cannot be resolved peacefully by mediation between employer and employees, female lawyer skilled for the labor law starts up judicial proceedings. Some characteristic cases of discrimination of women from the practice of SOS telephone, such as dismissal from the work, physical violence and sexual blackmail, are presented in the paper.

Expansion of the SOS regulon of Vibrio cholerae through extensive transcriptome analysis and experimental validation.

Science.gov (United States)

Krin, Evelyne; Pierlé, Sebastian Aguilar; Sismeiro, Odile; Jagla, Bernd; Dillies, Marie-Agnès; Varet, Hugo; Irazoki, Oihane; Campoy, Susana; Rouy, Zoé; Cruveiller, Stéphane; Médigue, Claudine; Coppée, Jean-Yves; Mazel, Didier

2018-05-21

The SOS response is an almost ubiquitous response of cells to genotoxic stresses. The full complement of genes in the SOS regulon for Vibrio species has only been addressed through bioinformatic analyses predicting LexA binding box consensus and in vitro validation. Here, we perform whole transcriptome sequencing from Vibrio cholerae treated with mitomycin C as an SOS inducer to characterize the SOS regulon and other pathways affected by this treatment. Comprehensive transcriptional profiling allowed us to define the full landscape of promoters and transcripts active in V. cholerae. We performed extensive transcription start site (TSS) mapping as well as detection/quantification of the coding and non-coding RNA (ncRNA) repertoire in strain N16961. To improve TSS detection, we developed a new technique to treat RNA extracted from cells grown in various conditions. This allowed for identification of 3078 TSSs with an average 5'UTR of 116 nucleotides, and peak distribution between 16 and 64 nucleotides; as well as 629 ncRNAs. Mitomycin C treatment induced transcription of 737 genes and 28 ncRNAs at least 2 fold, while it repressed 231 genes and 17 ncRNAs. Data analysis revealed that in addition to the core genes known to integrate the SOS regulon, several metabolic pathways were induced. This study allowed for expansion of the Vibrio SOS regulon, as twelve genes (ubiEJB, tatABC, smpA, cep, VC0091, VC1190, VC1369-1370) were found to be co-induced with their adjacent canonical SOS regulon gene(s), through transcriptional read-through. Characterization of UV and mitomycin C susceptibility for mutants of these newly identified SOS regulon genes and other highly induced genes and ncRNAs confirmed their role in DNA damage rescue and protection. We show that genotoxic stress induces a pervasive transcriptional response, affecting almost 20% of the V. cholerae genes. We also demonstrate that the SOS regulon is larger than previously known, and its syntenic organization is

A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition.

Science.gov (United States)

Krishnan, Anuradha; Abdullah, Tasduq Sheikh; Mounajjed, Taofic; Hartono, Stella; McConico, Andrea; White, Thomas; LeBrasseur, Nathan; Lanza, Ian; Nair, Sreekumaran; Gores, Gregory; Charlton, Michael

2017-06-01

The sequence of events that lead to inflammation and fibrosing nonalcoholic steatohepatitis (NASH) is incompletely understood. Hence, we investigated the chronology of whole body, tissue, and cellular events that occur during the evolution of diet-induced NASH. Male C57Bl/6 mice were assigned to a fast-food (FF; high calorie, high cholesterol, high fructose) or standard-chow (SC) diet over a period of 36 wk. Liver histology, body composition, mitochondrial respiration, metabolic rate, gene expression, and hepatic lipid content were analyzed. Insulin resistance [homeostasis model assessment-insulin resistance (HOMA-IR)] increased 10-fold after 4 wk. Fibrosing NASH was fully established by 16 wk. Total hepatic lipids increased by 4 wk and remained two- to threefold increased throughout. Hepatic triglycerides declined from sixfold increase at 8 wk to threefold increase by 36 wk. In contrast, hepatic cholesterol levels steadily increased from baseline at 8 wk to twofold by 36 wk. The hepatic immune cell population altered over time with macrophages persisting beyond 16 wk. Mitochondrial oxygen flux rates of FF mice diet were uniformly lower with all the tested substrates (13-276 pmol·s -1 ·ml -1 per unit citrate synthase) than SC mice (17-394 pmol·s -1 ·ml -1 per unit citrate synthase) and was accompanied by decreased mitochondrial:nuclear gene copy number ratios after 4 wk. Metabolic rate was lower in FF mice. Mitochondrial glutathione was significantly decreased at 24 wk in FF mice. Expression of dismutases and catalase was also decreased in FF mice. The evolution of NASH in the FF diet-induced model is multiphasic, particularly in terms of hepatic lipid composition. Insulin resistance precedes hepatic inflammation and fibrosis. Mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent. Collectively, these observations provide a unique overview of the sequence of changes that coevolve with the histological evolution of

Genetic analysis of the SOS response of Escherichia coli

International Nuclear Information System (INIS)

Mount, D.W.; Wertman, K.F.; Ennis, D.G.; Peterson, K.R.; Fisher, B.L.; Lyons, G.

1983-01-01

In the SOS response, a large number of E. coli genes having different functions are derepressed when the cellular DNA is damaged. This derepression occurs through inactivation of a repressor, the product of the lexA gene, by a protease activity of the recA gene product. The protease is thought to be activated in response to changes in DNA metabolism which follow the damage. After the SOS functions have acted, the protease activity declines and repression is again established. Because the DNA sequence of both lexA and recA have been determined, it is possible to induce many mutations in their regulatory and structural regions in order to analyze further the control of the SOS response. We are studying the effects of mutations in both the lexA and recA regulatory regions, and mutations which affect the protease activity or the sensitivity of repressor to the protease. Finally, we are using genetic methods to analyze a newly identified requirement for recA protein, induced mutagenesis in cells lacking repressor. 16 references, 3 figures

Phenomenology of an inducible mutagenic DNA repair pathway in Escherichia coli: SOS repair hypothesis

International Nuclear Information System (INIS)

Radman, M.

1974-01-01

A hypothesis is proposed according to which E. coli possesses an inducible DNA repair system. This hypothetical repair, which we call SOS repair, is manifested only following damage to DNA, and requires de novo protein synthesis. SOS repair in E. coli requires some known genetic elements: recA + , lex + and probably zab + . Mutagenesis by ultraviolet light is observed only under conditions of functional SOS repair: we therefore suspect that this is a mutation-prone repair. A number of phenomena and experiments is reviewed which at this point can best be interpreted in terms of an inducible mutagenic DNA repair system. Two recently discovered phenomena support the proposed hypothesis: existence of a mutant (tif) which, after a shift to elevated temperature, mimicks the effect of uv irradiation in regard to repair of phage lambda and uv mutagenesis, apparent activation of SOS repair by introduction into the recipient cell of damaged plasmid or Hfr DNA. Several specific predictions based on SOS repair hypothesis are presented in order to stimulate further experimental tests. (U.S.)

Technetium-99m labelled hydrazinonicotinamido human non-specific polyclonal immunoglobulin G for detection of infectious foci: a comparison with two other technetium-labelled immunoglobulin preparations

Energy Technology Data Exchange (ETDEWEB)

Claessens, R.A.M.J. [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Boerman, O.C. [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Koenders, E.B. [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Oyen, W.J.G. [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Meer, J.W.M. van der [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Corstens, F.H.M. [University Hospital Nijmegen, Department of Nuclear Medicine, P.O. Box 9101, 6500 HB Nijmegen (Netherlands)

1996-04-01

In this study we compared the tissue distribution of three different {sup 99m}Tc-hIgG preparations in groups of five Wistar rats with a focal intramuscular infection with Staphylococcus aureus. We compared {sup 99m}Tc-HYNIC-hIgG with {sup 99m}Tc-hIgG labelled via the so-called Schwarz method (reduction of disulphide bonds) and with the {sup 99m}Tc-labelled commercially available Technescan-HIG. Unlike the HYNIC linker, in the two other labelling methods free sulph-hydryl groups are involved in the binding of {sup 99m}Tc. High-performance liquid chromatography analysis of the labelled preparations and of plasma samples revealed aggregate or polymer formation in all three agents; this was least pronounced in the product labelled by means of the Schwarz method. The tested preparations did not show signs of degradation in vitro. The difference in linker chemistry was reflected in the tissue distribution. Thus the biodistribution of {sup 99m}Tc-HYNIC-hIgG was significantly different from the distribution of the two other preparations: abscess (1.4%{+-}0.2%ID/g), muscle, liver, spleen, plasma, lung, bone marrow, and small intestine concentrations were higher at 24 h p.i.; kidney uptake (1.19%{+-}0.08%ID/g) was significantly lower. The abscess-to-plasma and the abscess-to-muscle ratios (0.5 and 11, respectively), however, were in the same range for the three preparations tested. Quantitative analysis of the scintigraphs revealed that the total body clearance of {sup 99m}Tc-HYNIC-hIgG was significantly slower than for the other agents. The abscess uptake of {sup 99m}Tc-HYNIC-hIgG as a percentage of the remaining body activity was significantly higher. Based on its high abscess uptake, its low uptake in the kidneys and the high percentage of its abscess uptake in relation to the remaining body activity, we conclude that {sup 99m}Tc-HYNIC-hIgG seems superior to the two other preparations tested for the detection of infections. (orig.). With 7 figs., 2 tabs.

SOS gene induction and possible mutagenic effects of freeze-drying in Escherichia coli and Salmonella typhimurium.

Science.gov (United States)

Rosen, Rachel; Buchinger, Sebastian; Pfänder, Ramona; Pedhazur, Rami; Reifferscheid, Georg; Belkin, Shimshon

2016-11-01

We report the results of a study of the potential negative effects of the freeze-drying process, normally considered a benign means for long-term conservation of living cells and the golden standard in bacterial preservation. By monitoring gene induction using a whole-cell Escherichia coli bioreporter panel, in which diverse stress-responsive gene promoters are fused to luminescent or fluorescent reporting systems, we have demonstrated that DNA repair genes belonging to the SOS operon (recA, sulA, uvrA, umuD, and lexA) were induced upon resuscitation from the freeze-dried state, whereas other stress-responsive promoters such as grpE, katG, phoA, soxS, and sodA were not affected. This observation was confirmed by the UMU-chromotest (activation of the umuD gene promoter) in Salmonella typhimurium, as well as by real-time PCR analyses of selected E. coli SOS genes. We further show that a functional SOS operon is important in viability maintenance following resuscitation, but that at the same time, this repair system may introduce significantly higher mutation rates, comparable to those induced by high concentrations of a known mutagen. Our results also indicate that the entire freeze-drying process, rather than either freezing or drying separately, is instrumental in the induction of DNA damage.

Genetic requirements for high constitutive SOS expression in recA730 mutants of Escherichia coli.

Science.gov (United States)

Vlašić, Ignacija; Šimatović, Ana; Brčić-Kostić, Krunoslav

2011-09-01

The RecA protein in its functional state is in complex with single-stranded DNA, i.e., in the form of a RecA filament. In SOS induction, the RecA filament functions as a coprotease, enabling the autodigestion of the LexA repressor. The RecA filament can be formed by different mechanisms, but all of them require three enzymatic activities essential for the processing of DNA double-stranded ends. These are helicase, 5'-3' exonuclease, and RecA loading onto single-stranded DNA (ssDNA). In some mutants, the SOS response can be expressed constitutively during the process of normal DNA metabolism. The RecA730 mutant protein is able to form the RecA filament without the help of RecBCD and RecFOR mediators since it better competes with the single-strand binding (SSB) protein for ssDNA. As a consequence, the recA730 mutants show high constitutive SOS expression. In the study described in this paper, we studied the genetic requirements for constitutive SOS expression in recA730 mutants. Using a β-galactosidase assay, we showed that the constitutive SOS response in recA730 mutants exhibits different requirements in different backgrounds. In a wild-type background, the constitutive SOS response is partially dependent on RecBCD function. In a recB1080 background (the recB1080 mutation retains only helicase), constitutive SOS expression is partially dependent on RecBCD helicase function and is strongly dependent on RecJ nuclease. Finally, in a recB-null background, the constitutive SOS expression of the recA730 mutant is dependent on the RecJ nuclease. Our results emphasize the importance of the 5'-3' exonuclease for high constitutive SOS expression in recA730 mutants and show that RecBCD function can further enhance the excellent intrinsic abilities of the RecA730 protein in vivo. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Preparation of 99''m technitium labelled erythrocytes coated with anti-rhesus-D immunoglobulin (anti-Rho-D IgG) for defective spleen diagnosis

International Nuclear Information System (INIS)

Nanny Kartini, H.; Karnama, S.; Ahmad Muhtadi; Karna Awangga

1999-01-01

Preparation of 99m technetium-red blood cells coated with anti-rhesus-D IgG has been carried out and evaluated. Some factors such as the concentration of Sn(II) and incubation time which can influence the labelling yield are discussed. A labelling efficiency of greater than 90% (93.1 ±1.4% ) was obtained. Biological studies in normal human volunteers, showed that 99m Tc-red blood cell coated with anti-rhesus-D IgG accumulated in the spleen and may become a spleen imaging agent. (author)

Paraísos fiscales en la globalización financiera

Directory of Open Access Journals (Sweden)

Alberto Garzón Espinosa

2011-10-01

Full Text Available Los paraísos fiscales son espacios financieros caracterizados ante todo por su baja o nula tributación. En este artículo examinaremos con detalle el uso de los mismos por parte de los agentes económicos, centrándonos especialmente en los bancos y los fondos de inversión colectiva. No obstante, como elementos clave de un nuevo contexto financiero los paraísos fiscales han tenido un papel fundamental en la gestación y expansión de todas las crisis financieras recientes, razón por la cual también estudiaremos las consecuencias que la existencia misma de los paraísos fiscales tiene sobre la economía y el sistema financiero.Palabras clave: Paraísos fiscales, globalización financiera, neoliberalismo_______________Abstract:The tax haven are financial spaces which it characterize for its shorts taxations. In this article we will analyze the use of that by the economic agent, specially the banks and the funds of collective investment. However, like key elements of the new financial context, the tax haven was been a leading role in gestation and expansion of all financial crisis of our days. For that, we will study the consequences of this fact in the economy and financial system.Keywords: tax haven, financial globalization, neoliberalism.

Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model

Directory of Open Access Journals (Sweden)

Arianne van Koppen

2018-01-01

Conclusions: An early predictive molecular signature was identified that marked the active profibrotic process before histopathologic fibrosis becomes manifest. Early detection of the onset of NASH and fibrosis enables identification of novel blood-based biomarkers to stratify patients at risk, development of new therapeutics, and help shorten (preclinical experimental time frames.

32 CFR 99.1 - Scope and purpose.

Science.gov (United States)

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Scope and purpose. 99.1 Section 99.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN PROCEDURES FOR STATES AND LOCALITIES TO REQUEST INDEMNIFICATION § 99.1 Scope and purpose. (a) The Department...

Complex structures in the Nash-Moser category

DEFF Research Database (Denmark)

Gravesen, Jens

1989-01-01

Working in the Nash-Moser category, it is shown that the harmonic and holomorphic differentials and the Weierstrass points on a closed Riemann surface depend smoothly on the complex structure. It is also shown that the space of complex structures on any compact surface forms a principal bundle over...

Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange.

Science.gov (United States)

Burns, Michael C; Sun, Qi; Daniels, R Nathan; Camper, DeMarco; Kennedy, J Phillip; Phan, Jason; Olejniczak, Edward T; Lee, Taekyu; Waterson, Alex G; Rossanese, Olivia W; Fesik, Stephen W

2014-03-04

Aberrant activation of the small GTPase Ras by oncogenic mutation or constitutively active upstream receptor tyrosine kinases results in the deregulation of cellular signals governing growth and survival in ∼30% of all human cancers. However, the discovery of potent inhibitors of Ras has been difficult to achieve. Here, we report the identification of small molecules that bind to a unique pocket on the Ras:Son of Sevenless (SOS):Ras complex, increase the rate of SOS-catalyzed nucleotide exchange in vitro, and modulate Ras signaling pathways in cells. X-ray crystallography of Ras:SOS:Ras in complex with these molecules reveals that the compounds bind in a hydrophobic pocket in the CDC25 domain of SOS adjacent to the Switch II region of Ras. The structure-activity relationships exhibited by these compounds can be rationalized on the basis of multiple X-ray cocrystal structures. Mutational analyses confirmed the functional relevance of this binding site and showed it to be essential for compound activity. These molecules increase Ras-GTP levels and disrupt MAPK and PI3K signaling in cells at low micromolar concentrations. These small molecules represent tools to study the acute activation of Ras and highlight a pocket on SOS that may be exploited to modulate Ras signaling.

Validation of the Chinese Version of the Sense of Self (SOS) Scale

Science.gov (United States)

King, Ronnel B.; Ganotice, Fraide A., Jr.; Watkins, David A.

2012-01-01

This study explored the cross-cultural applicability of the Sense of Self (SOS) Scale in the Hong Kong Chinese cultural context. The SOS Scale is a 26-item questionnaire designed to measure students' sense of purpose, self-reliance, and self-concept in school. Six hundred ninety-seven Hong Kong Chinese high school students participated in the…

Intravenous aminohydroxypropylidene bisphosphonate does not modify 99mTc-hydroxymethylene bisphosphonate bone scintigraphy. A prospective study

International Nuclear Information System (INIS)

Macro, M.; Bouvard, G.; Le Gangneux, E.; Colin, T.; Loyau, G.

1995-01-01

Bisphosphonates have market affinity for bone that makes them useful in both the treatment and imaging of bone lesions. Bone scintigraphy is very sensitive for the detection of bone metastases, which can cause life-threatening hypercalcemia requiring emergency treatment. This prospective study was done to determine whether intravenous administration of pamidronate, a second-generation bisphophonate used to treat hypercalcemia, affects the affinity of the radiopharmaceutical 99m technetium-labeled hydroxymethylene bisphosphonate (99m Tc- HMDP) for bone and bone lesions. Six patients with metastatic bone disease and five with Paget's disease of bone had a 99m Tc-HMDP bone scan before and two to four days after an intravenous infusion of pamidronate. The number and activity of metastatic bone lesions were unchanged after pamidronate, even when the second bone scan was done only 24 hours after the pamidronate infusion. Our data suggest that emergency treatment of life-threatening hypercalcemia by intravenous pamidronate does not decrease the sensitivity of subsequent bone scanning done to detect bone metastases. (authors). 17 refs. 1 tab. 2 figs

45 CFR 99.1 - Scope of rules.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Scope of rules. 99.1 Section 99.1 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROCEDURE FOR HEARINGS FOR THE CHILD CARE AND DEVELOPMENT FUND General § 99.1 Scope of rules. (a) The rules of procedure in this section govern the practice...

Functional consequences of inducible genetic elements from the p53 SOS response in a mammalian organ system.

Science.gov (United States)

Guthrie, O'neil W

2017-10-01

In response to DNA damage from ultraviolet (UV) radiation, bacteria deploy the SOS response in order to limit cell death. This bacterial SOS response is characterized by an increase in the recA gene that transactivates expression of multiple DNA repair genes. The current series of experiments demonstrate that a mammalian organ system (the cochlea) that is not evolutionarily conditioned to UV radiation can elicit SOS responses that are reminiscent of that of bacteria. This mammalian SOS response is characterized by an increase in the p53 gene with activation of multiple DNA repair genes that harbor p53 response elements in their promoters. Furthermore, the experimental results provide support for the notion of a convergent trigger paradox, where independent SOS triggers facilitate disparate physiologic sequelae (loss vs. recovery of function). Therefore, it is proposed that the mammalian SOS response is multifunctional and manipulation of this endogenous response could be exploited in future biomedical interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of a novel streptococcal gene cassette mediating SOS mutagenesis in Streptococcus uberis

NARCIS (Netherlands)

Varhimo, Emilia; Savijoki, Kirsi; Jalava, Jari; Kuipers, Oscar P.; Varmanen, Pekka

Streptococci have been considered to lack the classical SOS response, defined by increased mutation after UV exposure and regulation by LexA. Here we report the identification of a potential self-regulated SOS mutagenesis gene cassette in the Streptococcaceae family. Exposure to UV light was found

Nash equilibria in noncooperative predator-prey games

Czech Academy of Sciences Publication Activity Database

Ramos, A. M.; Roubíček, Tomáš

2007-01-01

Roč. 56, č. 2 (2007), s. 211-241 ISSN 0095-4616 Grant - others:GA ČR(CZ) GA201/03/0934 Institutional research plan: CEZ:AV0Z10750506 Keywords : Reaction-diffusion system * Lotka-Voltera system * Nash equilibrium Subject RIV: BA - General Mathematics Impact factor: 0.873, year: 2007

The Embedding Theorems of Whitney and Nash

Indian Academy of Sciences (India)

We begin by briefly motivating the idea of amanifold and then discuss the embedding theorems of Whitney and Nash that allow us toview these objects inside appropriately large Euclidean spaces. Resonance – Journal of Science Education. Current Issue : Vol. 23, Issue 4. Current Issue Volume 23 | Issue 4. April 2018.

Comparative study of gated myocardial perfusion imaging using 99Tcm-tetrofosmin and 99Tcm-sestamibi

International Nuclear Information System (INIS)

Wang Ruihua; Ruan Qiao; Sun Ke; Han Xingmin; Sun Bingqi; Xie Xinli; Cheng Bing; Chen Yanlin; Liu Baoping

2013-01-01

Objective: To compare the results of 99 Tc m -tetrofosmin (TF) and 99 Tc m -MIBI G-MPI in evaluating left ventricular myocardial perfusion and other functional parameters. Methods: TF and MIBI were both labeled by 99 Tc m and the radiochemical purities were tested. During December 2011 to May 2012, 112 patients who had examinations of CAG and echocardiograph in one week after G-MPI were divided into 99 Tc m -TF group (47 patients) and 99 Tc m -MIBI group (65 patients) by simple random sampling. Patients who suffered from severe arrhythmia, clinically suspicious of myocarditis or cardiomyopathy were excluded. The research was approved by the ethics committee, and all patients signed informed consents. One-day 99 Tc m -TF G-MPI and two-day 99 Tc m -MIBI G-MPI were performed. The left ventricular functional parameters were acquired automatically by Cedars quantitative gated SPECT (QGS) software, including LVEF, EDV, ESV, peak filling rate (PFR), peak ejection rate (PER) and phase standard difference (SD). The data were analyzed using χ 2 test, two-sample t test, paired t test and linear correlation analysis by SPSS 17.0. Results: The radiochemical purities of 99 Tc m -TF and 99 Tc m -MIBI were (97.5±0.4) % and (99.1±0.2) % respectively. The coincidence rates of 99 Tc m -TF and 99 Tc m -MIBI G-MPI with CAG were 88.9% (40/45) and 90.5% (57/63), respectively. There was no significant difference between G-MPI results of the two agents (χ 2 =0.389, P>0.05). There was also no significant difference between left ventricular functional parameters of the two agents (LVEF:(62.60±13.56)% vs (60.52±7.08)%, t=0.940; EDV: (103.3±17.29) ml vs (98.52±19.37) ml, t=1.348; ESV: (41.73±12.69) ml vs (46.05±10.81) ml, t=0.851; PER: (2.73±0.67)EDV/s vs (2.61±1.04) EDV/s, t=0.725; PFR: (2.13±0.80) EDV/s vs (2.07±1.09) EDV/s, t=0.339; phase SD: (5.58±4.16)° vs (5.97±4.64)°, t=0.450; all P>0.05). There was no significant difference between left ventricular functional

SOS score: an optimized score to screen acute stroke patients for obstructive sleep apnea.

Science.gov (United States)

Camilo, Millene R; Sander, Heidi H; Eckeli, Alan L; Fernandes, Regina M F; Dos Santos-Pontelli, Taiza E G; Leite, Joao P; Pontes-Neto, Octavio M

2014-09-01

Obstructive sleep apnea (OSA) is frequent in acute stroke patients, and has been associated with higher mortality and worse prognosis. Polysomnography (PSG) is the gold standard diagnostic method for OSA, but it is impracticable as a routine for all acute stroke patients. We evaluated the accuracy of two OSA screening tools, the Berlin Questionnaire (BQ), and the Epworth Sleepiness Scale (ESS) when administered to relatives of acute stroke patients; we also compared these tools against a combined screening score (SOS score). Ischemic stroke patients were submitted to a full PSG at the first night after onset of symptoms. OSA severity was measured by apnea-hypopnea index (AHI). BQ and ESS were administered to relatives of stroke patients before the PSG and compared to SOS score for accuracy and C-statistics. We prospectively studied 39 patients. OSA (AHI ≥10/h) was present in 76.9%. The SOS score [area under the curve (AUC): 0.812; P = 0.005] and ESS (AUC: 0.789; P = 0.009) had good predictive value for OSA. The SOS score was the only tool with significant predictive value (AUC: 0.686; P = 0.048) for severe OSA (AHI ≥30/h), when compared to ESS (P = 0.119) and BQ (P = 0.191). The threshold of SOS ≤10 showed high sensitivity (90%) and negative predictive value (96.2%) for OSA; SOS ≥20 showed high specificity (100%) and positive predictive value (92.5%) for severe OSA. The SOS score administered to relatives of stroke patients is a useful tool to screen for OSA and may decrease the need for PSG in acute stroke setting. Copyright © 2014 Elsevier B.V. All rights reserved.

SOS Children's Friendly Community Historical Overview

Science.gov (United States)

Lukaš, Mirko; Lenard, Ivan

2014-01-01

SOS Children's Village Croatia is categorized as a children's home whose primary goal is taking care of children without an adequate parental care or parents themselves. Moreover, it aims at providing children, regardless of their racial, national or religious affiliation, with affection and love in a safe family environment. In addition, SOS…

On defense strategies for system of systems using aggregated correlations

Energy Technology Data Exchange (ETDEWEB)

Rao, Nageswara S. [ORNL; Imam, Neena [ORNL; Ma, Chris Y. T. [Hang Seng Management College, Hon Kong; Hausken, Kjell [University of Stavanger, Norway; He, Fei [Texas A& M University, Kingsville, TX, USA; Zhuang, Jun [University at Buffalo (SUNY)

2017-04-01

We consider a System of Systems (SoS) wherein each system Si, i = 1; 2; ... ;N, is composed of discrete cyber and physical components which can be attacked and reinforced. We characterize the disruptions using aggregate failure correlation functions given by the conditional failure probability of SoS given the failure of an individual system. We formulate the problem of ensuring the survival of SoS as a game between an attacker and a provider, each with a utility function composed of asurvival probability term and a cost term, both expressed in terms of the number of components attacked and reinforced. The survival probabilities of systems satisfy simple product-form, first-order differential conditions, which simplify the Nash Equilibrium (NE) conditions. We derive the sensitivity functions that highlight the dependence of SoS survival probability at NE on cost terms, correlation functions, and individual system survival probabilities.We apply these results to a simplified model of distributed cloud computing infrastructure.

Anti-CD20 Immunoglobulin G Radiolabeling with a 99mTc-Tricarbonyl Core: In Vitro and In Vivo Evaluations.

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Hélène Carpenet

Full Text Available In recent years, the diagnostic and therapeutic uses of radioisotopes have shown significant progress. Immunoglobulin (Ig appears to be a promising tracer, particularly due to its ability to target selected antigens. The main objective of this study is to optimize and assess an Ig radiolabeling method with Technetium 99m (99mTc, an attractive radioelement used widely for diagnostic imaging. Monoclonal anti-CD20 IgG was retained to study in vitro and in vivo radiolabeling impact. After IgG derivatization with 2-iminothiolane, IgG-SH was radiolabeled by an indirect method, using a 99mTc-tricarbonyl core. Radiolabeling stability was evaluated over 24h by thin-layer chromatography. IgG integrity was checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with Western blot and autoradiography. The radiolabeled Ig's immunoaffinity was assessed in vitro by a radioimmunoassay method and binding experiments with cells (EL4-hCD20 and EL4-WT. Biodistribution studies were performed in normal BALB/c mice. Tumor uptake was assessed in mice bearing EL4-hCD20 and EL4-WT subcutaneous xenografts. With optimized method, high radiolabeling yields were obtained (95.9 ± 3.5%. 99mTc-IgG-SH was stable in phosphate-buffered saline (4°C and 25°C and in serum (37°C, even if important sensitivity to transchelation was observed. IgG was not degraded by derivatization and radiolabeling, as shown by Western blot and autoradiography results. 99mTc-anti-CD20 IgG-SH immunoaffinity was estimated with Kd = 35 nM by both methods. In vivo biodistribution studies for 48h showed significant accumulation of radioactivity in plasma, liver, spleen, lungs and kidneys. Planar scintigraphy of mice bearing tumors showed a significant uptake of 99mTc-anti-CD20 IgG-SH in CD20+ tumor versus CD20- tumor. Radiolabeling of derivatized IgG with 99mTc-tricarbonyl was effective, stable and required few antibody amounts. This attractive radiolabeling method is "antibody safe

Computing the Pareto-Nash equilibrium set in finite multi-objective mixed-strategy games

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Victoria Lozan

2013-10-01

Full Text Available The Pareto-Nash equilibrium set (PNES is described as intersection of graphs of efficient response mappings. The problem of PNES computing in finite multi-objective mixed-strategy games (Pareto-Nash games is considered. A method for PNES computing is studied. Mathematics Subject Classification 2010: 91A05, 91A06, 91A10, 91A43, 91A44.

Loss of miR-141/200c ameliorates hepatic steatosis and inflammation by reprogramming multiple signaling pathways in NASH

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Tran, Melanie; Lee, Sang-Min; Shin, Dong-Ju

2017-01-01

Accumulation of lipid droplets and inflammatory cell infiltration is the hallmark of nonalcoholic steatohepatitis (NASH). The roles of noncoding RNAs in NASH are less known. We aim to elucidate the function of miR-141/200c in diet-induced NASH. WT and miR-141/200c–/– mice were fed a methionine and choline deficient (MCD) diet for 2 weeks to assess markers of steatosis, liver injury, and inflammation. Hepatic miR-141 and miR-200c RNA levels were highly induced in human patients with NASH fatty liver and in WT MCD mice. miR-141/200c–/– MCD mice had reduced liver weights and triglyceride (TG) levels, which was associated with increased microsomal TG transfer protein (MTTP) and PPARα but reduced SREBP1c and FAS expression. Inflammation was attenuated and F4/80 macrophage activation was suppressed in miR-141/200c–/– mice, as evidenced by decreased serum aminotransferases and IL-6 and reduced hepatic proinflammatory, neutrophil, and profibrotic genes. Treatment with LPS in BM-derived macrophages isolated from miR-200c/141–/– mice polarized macrophages toward the M2 antiinflammatory state by increasing Arg1 and IL-10 levels while decreasing the M1 marker iNOS. In addition, elevated phosphorylated AMPK (p-AMPK), p-AKT, and p-GSK3β and diminished TLR4 and p-mTOR/p-4EBP1 proteins were observed. Lipidomics and metabolomics revealed alterations of TG and phosphatidylcholine (PC) lipid species by miR-141/200c deficiency. In summary, miR-141/200c deficiency diminished NASH-associated hepatic steatosis and inflammation by reprogramming lipid and inflammation signaling pathways. PMID:29093267

Atomic orbital-based SOS-MP2 with tensor hypercontraction. II. Local tensor hypercontraction

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Song, Chenchen; Martínez, Todd J.

2017-01-01

In the first paper of the series [Paper I, C. Song and T. J. Martinez, J. Chem. Phys. 144, 174111 (2016)], we showed how tensor-hypercontracted (THC) SOS-MP2 could be accelerated by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs). This reduced the formal scaling of the SOS-MP2 energy calculation to cubic with respect to system size. The computational bottleneck then becomes the THC metric matrix inversion, which scales cubically with a large prefactor. In this work, the local THC approximation is proposed to reduce the computational cost of inverting the THC metric matrix to linear scaling with respect to molecular size. By doing so, we have removed the primary bottleneck to THC-SOS-MP2 calculations on large molecules with O(1000) atoms. The errors introduced by the local THC approximation are less than 0.6 kcal/mol for molecules with up to 200 atoms and 3300 basis functions. Together with the graphical processing unit techniques and locality-exploiting approaches introduced in previous work, the scaled opposite spin MP2 (SOS-MP2) calculations exhibit O(N2.5) scaling in practice up to 10 000 basis functions. The new algorithms make it feasible to carry out SOS-MP2 calculations on small proteins like ubiquitin (1231 atoms/10 294 atomic basis functions) on a single node in less than a day.

Novel Escherichia coli umuD′ Mutants: Structure-Function Insights into SOS Mutagenesis

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McLenigan, Mary; Peat, Thomas S.; Frank, Ekaterina G.; McDonald, John P.; Gonzalez, Martín; Levine, Arthur S.; Hendrickson, Wayne A.; Woodgate, Roger

1998-01-01

Although it has been 10 years since the discovery that the Escherichia coli UmuD protein undergoes a RecA-mediated cleavage reaction to generate mutagenically active UmuD′, the function of UmuD′ has yet to be determined. In an attempt to elucidate the role of UmuD′ in SOS mutagenesis, we have utilized a colorimetric papillation assay to screen for mutants of a hydroxylamine-treated, low-copy-number umuD′ plasmid that are unable to promote SOS-dependent spontaneous mutagenesis. Using such an approach, we have identified 14 independent umuD′ mutants. Analysis of these mutants revealed that two resulted from promoter changes which reduced the expression of wild-type UmuD′, three were nonsense mutations that resulted in a truncated UmuD′ protein, and the remaining nine were missense alterations. In addition to the hydroxylamine-generated mutants, we have subcloned the mutations found in three chromosomal umuD1, umuD44, and umuD77 alleles into umuD′. All 17 umuD′ mutants resulted in lower levels of SOS-dependent spontaneous mutagenesis but varied in the extent to which they promoted methyl methanesulfonate-induced mutagenesis. We have attempted to correlate these phenotypes with the potential effect of each mutation on the recently described structure of UmuD′. PMID:9721309

Specificity determinants for autoproteolysis of LexA, a key regulator of bacterial SOS mutagenesis.

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Mo, Charlie Y; Birdwell, L Dillon; Kohli, Rahul M

2014-05-20

Bacteria utilize the tightly regulated stress response (SOS) pathway to respond to a variety of genotoxic agents, including antimicrobials. Activation of the SOS response is regulated by a key repressor-protease, LexA, which undergoes autoproteolysis in the setting of stress, resulting in derepression of SOS genes. Remarkably, genetic inactivation of LexA's self-cleavage activity significantly decreases acquired antibiotic resistance in infection models and renders bacteria hypersensitive to traditional antibiotics, suggesting that a mechanistic study of LexA could help inform its viability as a novel target for combating acquired drug resistance. Despite structural insights into LexA, a detailed knowledge of the enzyme's protease specificity is lacking. Here, we employ saturation and positional scanning mutagenesis on LexA's internal cleavage region to analyze >140 mutants and generate a comprehensive specificity profile of LexA from the human pathogen Pseudomonas aeruginosa (LexAPa). We find that the LexAPa active site possesses a unique mode of substrate recognition. Positions P1-P3 prefer small hydrophobic residues that suggest specific contacts with the active site, while positions P5 and P1' show a preference for flexible glycine residues that may facilitate the conformational change that permits autoproteolysis. We further show that stabilizing the β-turn within the cleavage region enhances LexA autoproteolytic activity. Finally, we identify permissive positions flanking the scissile bond (P4 and P2') that are tolerant to extensive mutagenesis. Our studies shed light on the active site architecture of the LexA autoprotease and provide insights that may inform the design of probes of the SOS pathway.

Onderzoek naar de toepasbaarheid van SOS-chromotest

NARCIS (Netherlands)

Voogd CE; van der Stel JJ; Verharen HW; van Bruchem MC

1988-01-01

Met 35 stoffen werd de mutagene activiteit onderzocht met een SOS-chromotest kit, de Ames-test en de fluctuatietest met Klebsiella pneumoniae. Voorzover het alkylerende stoffen betreft die basenpaar substituties veroorzaken, blijkt er een goede overeenstemming te bestaan met de resultaten van

Nash equilibria in quantum games with generalized two-parameter strategies

International Nuclear Information System (INIS)

Flitney, Adrian P.; Hollenberg, Lloyd C.L.

2007-01-01

In the Eisert protocol for 2x2 quantum games [J. Eisert, et al., Phys. Rev. Lett. 83 (1999) 3077], a number of authors have investigated the features arising from making the strategic space a two-parameter subset of single qubit unitary operators. We argue that the new Nash equilibria and the classical-quantum transitions that occur are simply an artifact of the particular strategy space chosen. By choosing a different, but equally plausible, two-parameter strategic space we show that different Nash equilibria with different classical-quantum transitions can arise. We generalize the two-parameter strategies and also consider these strategies in a multiplayer setting

Survival and SOS response induction in ultraviolet B irradiated Escherichia coli cells with defective repair mechanisms.

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Prada Medina, Cesar Augusto; Aristizabal Tessmer, Elke Tatjana; Quintero Ruiz, Nathalia; Serment-Guerrero, Jorge; Fuentes, Jorge Luis

2016-06-01

Purpose In this paper, the contribution of different genes involved in DNA repair for both survival and SOS induction in Escherichia coli mutants exposed to ultraviolet B radiation (UVB, [wavelength range 280-315 nm]) was evaluated. Materials and methods E. coli strains defective in uvrA, oxyR, recO, recN, recJ, exoX, recB, recD or xonA genes were used to determine cell survival. All strains also had the genetic sulA::lacZ fusion, which allowed for the quantification of SOS induction through the SOS Chromotest. Results Five gene products were particularly important for survival, as follows: UvrA > RecB > RecO > RecJ > XonA. Strains defective in uvrA and recJ genes showed elevated SOS induction compared with the wild type, which remained stable for up to 240 min after UVB-irradiation. In addition, E. coli strains carrying the recO or recN mutation showed no SOS induction. Conclusions The nucleotide excision and DNA recombination pathways were equally used to repair UVB-induced DNA damage in E. coli cells. The sulA gene was not turned off in strains defective in UvrA and RecJ. RecO protein was essential for processing DNA damage prior to SOS induction. In this study, the roles of DNA repair proteins and their contributions to the mechanisms that induce SOS genes in E. coli are proposed.

DNA compaction in the early part of the SOS response is dependent on RecN and RecA.

Science.gov (United States)

Odsbu, Ingvild; Skarstad, Kirsten

2014-05-01

The nucleoids of undamaged Escherichia coli cells have a characteristic shape and number, which is dependent on the growth medium. Upon induction of the SOS response by a low dose of UV irradiation an extensive reorganization of the nucleoids occurred. Two distinct phases were observed by fluorescence microscopy. First, the nucleoids were found to change shape and fuse into compact structures at midcell. The compaction of the nucleoids lasted for 10-20 min and was followed by a phase where the DNA was dispersed throughout the cells. This second phase lasted for ~1 h. The compaction was found to be dependent on the recombination proteins RecA, RecO and RecR as well as the SOS-inducible, SMC (structural maintenance of chromosomes)-like protein RecN. RecN protein is produced in high amounts during the first part of the SOS response. It is possible that the RecN-mediated 'compact DNA' stage at the beginning of the SOS response serves to stabilize damaged DNA prior to recombination and repair.

Influence of the gene xthA in the activation of SOS response of Escherichia coli

International Nuclear Information System (INIS)

Dominguez M, V.

2013-01-01

The SOS response is one of the strategies that has Escherichia coli to counteract the lesions in the genetic material. The response is integrated for approximately 60 genes that when are activated they provide to the cell a bigger opportunity to survive. For the activation of this system is necessary that DNA regions of simple chain are generated, in such a way that most of the lesions should be processed, to be able to induce this answer. Some genes that intervene in this procedure, as recO, recB and recJ are recognized since when being exposed to the radiation, their activity SOS is smaller than in a wild strain. In previous works has been studied that to inactivate the genes that are involves in the lesions processing to generate DNA of simple chain, the SOS induction level diminishes with regard to a wild strain, but that when eliminating the genes that are involves directly in the repair, the SOS response increases. In this work a strain with defects in the gene xthA was built, which encodes for an endonuclease AP that participates in the repair mechanism by base excision and was evaluated their sensibility as the activity of the SOS response when exposing it to UV light and gamma radiation. The results showed that the lethality of the strain with the defect is very similar to the wild strain; while the activation level of the SOS response is bigger in comparison with the wild strain when being exposed to UV light; suggesting the existence of an enzyme that recognizes the lesions that produces this radiation, however, is not this the main repair channel, since the survival is similar to that of the wild strain. On the contrary, the results obtained with gamma radiation showed that the lethality diminishes in comparison to that of the wild strain, like the SOS activity; due surely to that the gene product intervenes in the repair for base excision, participating in the formation of the previous substrate to the activation of the SOS response. (Author)

Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate.

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Lee, Young Kwang; Low-Nam, Shalini T; Chung, Jean K; Hansen, Scott D; Lam, Hiu Yue Monatrice; Alvarez, Steven; Groves, Jay T

2017-04-28

The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) plays a critical role in signal transduction by activating Ras. Here we introduce a single-molecule assay in which individual SOS molecules are captured from raw cell lysate using Ras-functionalized supported membrane microarrays. This enables characterization of the full-length SOS protein, which has not previously been studied in reconstitution due to difficulties in purification. Our measurements on the full-length protein reveal a distinct role of the C-terminal proline-rich (PR) domain to obstruct the engagement of allosteric Ras independently of the well-known N-terminal domain autoinhibition. This inhibitory role of the PR domain limits Grb2-independent recruitment of SOS to the membrane through binding of Ras·GTP in the SOS allosteric binding site. More generally, this assay strategy enables characterization of the functional behaviour of GEFs with single-molecule precision but without the need for purification.

G+K 1Σ+/sub g/ double-minimum excited state of H2

International Nuclear Information System (INIS)

Glover, R.M.; Weinhold, F.

1977-01-01

We have obtained a Born--Oppenheimer potential curve for the previously uncharacterized third 1 Σ + /sub g/ state of H 2 , using a correlated 20-term wavefunction of generalized James--Coolidge type. We find this potential curve to have a double-minimum character, with the inner (Rydberg-like) and outer (''ionic'') wells having minima at about 1.99 and 3.30 bohr, respectively, and an intervening maximum at 2.76 bohr. Unlike the extensively studied E+F double-minimum state, the outer well here appears to be the deeper, by some 450 cm -1 in our calculation. The inner and outer minima can apparently be associated with spectral lines that in experimental tables have previously been attributed to distinct G and K electronic states. The appropriate spectroscopic term symbol of this combined state is accordingly G+K 1 Σ + /sub g/ (1ssigma3dsigma+2pπ 2 )

Study of Nash equilibrium by increasing game parameters in 3-player quantum game

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H Goudarzi

2013-03-01

Full Text Available  Using the quantum game formalism in 3-player system, we calculate the Nash equilibrium in quantum Prisoners’ Dilemma by increasing parameters of unitary operator. Since, the entanglement plays an important role in quantum states of particles quantum game, actually its effect on the obtained results of Nash equilibrium is investigated. It is shown that increasing the parameters enhances the game payoff function.

SOS System Induction Inhibits the Assembly of Chemoreceptor Signaling Clusters in Salmonella enterica.

Science.gov (United States)

Irazoki, Oihane; Mayola, Albert; Campoy, Susana; Barbé, Jordi

2016-01-01

Swarming, a flagellar-driven multicellular form of motility, is associated with bacterial virulence and increased antibiotic resistance. In this work we demonstrate that activation of the SOS response reversibly inhibits swarming motility by preventing the assembly of chemoreceptor-signaling polar arrays. We also show that an increase in the concentration of the RecA protein, generated by SOS system activation, rather than another function of this genetic network impairs chemoreceptor polar cluster formation. Our data provide evidence that the molecular balance between RecA and CheW proteins is crucial to allow polar cluster formation in Salmonella enterica cells. Thus, activation of the SOS response by the presence of a DNA-injuring compound increases the RecA concentration, thereby disturbing the equilibrium between RecA and CheW and resulting in the cessation of swarming. Nevertheless, when the DNA-damage decreases and the SOS response is no longer activated, basal RecA levels and thus polar cluster assembly are reestablished. These results clearly show that bacterial populations moving over surfaces make use of specific mechanisms to avoid contact with DNA-damaging compounds.

Endovascular stentectomy using the snare over stent-retriever (SOS technique: An experimental feasibility study.

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Tareq Meyer

Full Text Available Feasibility of endovascular stentectomy using a snare over stent-retriever (SOS technique was evaluated in a silicon flow model and an in vivo swine model. In vitro, stentectomy of different intracranial stents using the SOS technique was feasible in 22 out of 24 (92% retrieval maneuvers. In vivo, stentectomy was successful in 10 out of 10 procedures (100%. In one case self-limiting vasospasm was observed angiographically as a technique related complication in the animal model. Endovascular stentectomy using the SOS technique is feasible in an experimental setting and may be transferred to a clinical scenario.

Sos - response induction by gamma radiation in Escherichia coli strains with different repair capacities

International Nuclear Information System (INIS)

Serment Guerrero, J.H.

1992-01-01

The Sos - response in Escherichia coli is formed by several genes involved in mechanisms of tolerance and/or repair, and only activates when a DNA - damage appears. It is controlled by recA and lexA genes. In normal circumstances, LexA protein is linked in every Sos operators, blocking the transcription. When a DNA damage occurs, a Sos signal is generated, Rec A protein changes its normal functions, starts acting as a protease and cleaves Lex A, allowing the transcription of all Sos genes. This response can be quantified by means of Sos Chromo test, performed by Quillardet and Ofnung (1985). In using the Chromo test, it has been observed that the DNA damage made by gamma radiation in Escherichia coli depends on both the doses and the doses rate. It has been shown that the exposure of Escherichia coli PQ37 strain (uvrA) to low doses at low dose rate appears to retard the response, suggesting the action of a repair mechanism. (Brena 1990). In this work, we compare the response in Escherichia coli strains deficient in different mechanisms of repair and/or tolerance. It is observed the importance of rec N gene in the repair of DNA damage produced by gamma radiation. (Author)

Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP-1c Tg mice fed high-fat and high-fructose diet.

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Wada, Tsutomu; Miyashita, Yusuke; Sasaki, Motohiro; Aruga, Yusuke; Nakamura, Yuto; Ishii, Yoko; Sasahara, Masakiyo; Kanasaki, Keizo; Kitada, Munehiro; Koya, Daisuke; Shimano, Hitoshi; Tsuneki, Hiroshi; Sasaoka, Toshiyasu

2013-12-01

Because the renin-angiotensin-aldosterone system has been implicated in the development of insulin resistance and promotion of fibrosis in some tissues, such as the vasculature, we examined the effect of eplerenone, a selective mineralocorticoid receptor (MR) antagonist, on nonalcoholic steatohepatitis (NASH) and metabolic phenotypes in a mouse model reflecting metabolic syndrome in humans. We adopted liver-specific transgenic (Tg) mice overexpressing the active form of sterol response element binding protein-1c (SREBP-1c) fed a high-fat and fructose diet (HFFD) as the animal model in the present study. When wild-type (WT) C57BL/6 and liver-specific SREBP-1c Tg mice grew while being fed HFFD for 12 wk, body weight and epididymal fat weight increased in both groups with an elevation in blood pressure and dyslipidemia. Glucose intolerance and insulin resistance were also observed. Adipose tissue hypertrophy and macrophage infiltration with crown-like structure formation were also noted in mice fed HFFD. Interestingly, the changes noted in both genotypes fed HFFD were significantly ameliorated with eplerenone. HFFD-fed Tg mice exhibited the histological features of NASH in the liver, including macrovesicular steatosis and fibrosis, whereas HFFD-fed WT mice had hepatic steatosis without apparent fibrotic changes. Eplerenone effectively ameliorated these histological abnormalities. Moreover, the direct suppressive effects of eplerenone on lipopolysaccharide-induced TNFα production in the presence and absence of aldosterone were observed in primary-cultured Kupffer cells and bone marrow-derived macrophages. These results indicated that eplerenone prevented the development of NASH and metabolic abnormalities in mice by inhibiting inflammatory responses in both Kupffer cells and macrophages.

99mTc human IgG radiolabelled by HYNIC. Biodistribution and scintigraphy of experimentally induced inflammatory lesions in animal model

International Nuclear Information System (INIS)

Karczmarczyk, U.; Markiewicz, A.; Mikolajczak, R.; Michalik, J.; Lisiak, E.; Bilski, M.; Pietrzykowski, J.

2004-01-01

Our goal was the efficient labelling of highly purified human gammaglobulin. This radioactive protein fraction can be used as a basic compound of radiopharmaceutical formulation for inflammation lesion diagnosis. This application was experimentally illustrated in animal models with artificially induced inflammatory lesions after turpentine oil injection into mouse leg muscle. Hydrazine nicotinamine derivative of human gammaglobulin (IgG-HYNIC) was synthesized according to Abrams method. The radionuclide: technetium 99mT c has been introduced into protein molecules by indirect method incorporation in phosphate buffer, pH 7.4, in the presence of stannous chloride as a reducing agent for sodium pertechnetate, and EDTA as a coligand. Radiochemical purity was estimated by thin layer chromatography. The stability of labelled IgG-HYNIC derivative in human serum in presence of copper, cobalt, iron and manganese salts was analyzed by HPLC method (BioSEP SEC 4000, eluent: 0.1mol/L phosphate). Inflammation lesions were induced in Balb/3 mice muscles by injection of 0.2 ml turpentine oil into the leg muscle. Five days later, inflammation lesions were visualized by hIgG-HYNIC- 99mT c injections. The tracer accumulation in tissue was evaluated by gamma camera at 1 to 24 hour intervals. Efficiency of technetium 99mT c human gammaglobulin labelling (pH 7.4, temp. 37 o C) was strictly dependant on ligand and coligand presence in the reaction mixture. Labelling of IgG molecules without any supplements resulted in very low efficiency, never exceeding the range of 5%. Presence of EDTA or hydrazine nicotinamide (HYNIC) conjugated with IgG increased radiolabelling efficiency to 50%. IgG-HYNIC derivative in EDTA presence enables us to reach value above 95% radiochemical purity. Stability of IgG-HYNIC derivative labelled with technetium 99mT c decreased rapidly in serum in time - up to 70% of initial value in 30 minutes and only 20% during further 4 hr incubation. This means that as much

Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence*

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Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L.; Embrey, Kevin J.; Golovanov, Alexander P.

2016-01-01

The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly 15N-labeled Ras as well as [13C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. PMID:26565026

Overexpression of the PtSOS2 gene improves tolerance to salt stress in transgenic poplar plants.

Science.gov (United States)

Yang, Yang; Tang, Ren-Jie; Jiang, Chun-Mei; Li, Bei; Kang, Tao; Liu, Hua; Zhao, Nan; Ma, Xu-Jun; Yang, Lei; Chen, Shao-Liang; Zhang, Hong-Xia

2015-09-01

In higher plants, the salt overly sensitive (SOS) signalling pathway plays a crucial role in maintaining ion homoeostasis and conferring salt tolerance under salinity condition. Previously, we functionally characterized the conserved SOS pathway in the woody plant Populus trichocarpa. In this study, we demonstrate that overexpression of the constitutively active form of PtSOS2 (PtSOS2TD), one of the key components of this pathway, significantly increased salt tolerance in aspen hybrid clone Shanxin Yang (Populus davidiana × Populus bolleana). Compared to the wild-type control, transgenic plants constitutively expressing PtSOS2TD exhibited more vigorous growth and produced greater biomass in the presence of high concentrations of NaCl. The improved salt tolerance was associated with a decreased Na(+) accumulation in the leaves of transgenic plants. Further analyses revealed that plasma membrane Na(+) /H(+) exchange activity and Na(+) efflux in transgenic plants were significantly higher than those in the wild-type plants. Moreover, transgenic plants showed improved capacity in scavenging reactive oxygen species (ROS) generated by salt stress. Taken together, our results suggest that PtSOS2 could serve as an ideal target gene to genetically engineer salt-tolerant trees. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

77 FR 65896 - Award of a Single-Source Replacement Grant to SOS Children's Villages Illinois in Chicago, IL

Science.gov (United States)

2012-10-31

....623] Award of a Single-Source Replacement Grant to SOS Children's Villages Illinois in Chicago, IL... (FYSB) announces the award of a single-source replacement grant to SOS Children's Villages Illinois in... grant. ACYF/FYSB has designated SOS Children's Villages Illinois, a 501(c)(3) non-profit organization...

The -675 4G/5G polymorphism in the PAI-1 gene may not contribute to the risk of PCOS.

Science.gov (United States)

Zhang, T-T; Yuan, L; Yang, Y-M; Ren, Y

2014-08-01

The association between the -675 4G/5G polymorphism in PAI-1 gene and PCOS has been studied with inconclusive results. We sought to investigate this inconsistency by performing a comprehensive meta-analysis on the polymorphism. Searches were performed in the PubMed, Embase, CNKI and Wanfang databases, covering all papers. Statistical analysis was performed using Revman5.2 and STATA11.0 software. A total of 11 case-control studies were extracted on the polymorphism involving 1861 PCOS cases and 1187 controls. The results showed that, no significant increased/decreased risk were found for the polymorphism for PCOS: OR = 1.03, 95% CI = 0.77-1.66, p = 0.52 for 4G4G + 4G5G vs. 5G5G; OR = 0.99, 95% CI = 0.66-1.49, p = 0.96 for 4G4G vs. 5G5G + 4G5G; OR = 1.08, 95% CI = 0.66-1.79, p = 0.76 for 4G4G vs. 5G5G; OR = 1.11, 95% CI = 0.78-1.58, p = 0.56 for 4G5G vs. 5G5G; OR = 1.00, 95% CI = 0.71-1.41, p = 0.99 for 4G vs. 5G. In the further subgroup analysis by ethnicity, we did not find a significant association between the polymorphism for PCOS risk in either Asians or Europeans. Our findings demonstrated that -675 4G/5G polymorphism in the PAI-1 gene might not be a risk factor for the development of PCOS.

Computing Nash Equilibrium in Wireless Ad Hoc Networks

DEFF Research Database (Denmark)

Bulychev, Peter E.; David, Alexandre; Larsen, Kim G.

2012-01-01

This paper studies the problem of computing Nash equilibrium in wireless networks modeled by Weighted Timed Automata. Such formalism comes together with a logic that can be used to describe complex features such as timed energy constraints. Our contribution is a method for solving this problem...

Metabolic pathway analysis using a nash equilibrium approach

NARCIS (Netherlands)

Lucia, Angelo; DiMaggio, Peter A.; Alonso-Martinez, Diego

2018-01-01

A novel approach to metabolic network analysis using a Nash Equilibrium (NE) formulation is proposed in which enzymes are considered players in a multi-player game. Each player has its own payoff function with the objective of minimizing the Gibbs free energy associated with the biochemical

Peripheral Quantitative Computed Tomography (pQCT), Broad Band Ultrasound Attenuation (BUA) and Speed of Sound (SOS) in a population of normal females aged from 8 to 20 years

International Nuclear Information System (INIS)

Bagni, B.; Corazzari, T.; Bagni, I.; Garuti, F.; Franceschetto, A.; Casolo, A.; Pansini, F.

2002-01-01

Aim: To evaluate, in a population of young healthy females aged from 8 to 20 years the bone mass peak (or density), the normal ranges versus age and menarche-age using two method: pQCT (peripheral Quantitative Computed Tomography) and ultrasound absorptiometry. Material and Methods: From 1998 to 2000 selective measurement of Bone Mineral Density (BMD) of trabecular bone at the ultradistal radius using pQCT, BUA (Broad Band Attenuation) and SOS ( Speed Of Sound) was carried out on 426 healthy females (aged from 8 to 20 years) in north Italy. BMD were measured using a single photon miniaturized tomographic scanner in the ultradistal radius, SOS and BUA were measured at the same time, using a water bath device obtaining parametric bidimensional images of BUA and SOS. The population studied refers to normal females free of bone metabolism alteration, in pre and post-pubertal status. Results: A normal range of BMD, BUA and SOS versus age and menarche age were established. A linear correlation was found between BUA and BMD measured with pQCT. SOS does not show any correlation with BMD. The pre-puberty and the post-puberty groups show statistically significant differences between SOS, BUA and BMD. We found the peak bone density (measured with pQCT) in the trabecular bone at the ultradistal radius at 15 years of age (mean menarche age of 10 years). The same position of the peak was found for BUA, for SOS the situation is not well defined. The analytical fitting of the data highlights a polynomial correlation of BMD vs. age, SOS vs. age, BUA vs. age. Conclusions: It appears that the sexual growth influences the position of peak bone density. The results obtained show a statistically significant correlation between BUA and BMD versus age, the menarche-age and the period of exposure of bone tissue to the oestrogen. After all, pQCT and ultrasound are useful techniques to evaluate bone density and structure also in a growing population. The results of this study shows the

3, 3'-Diindolylmethane alleviates steatosis and the progression of NASH partly through shifting the imbalance of Treg/Th17 cells to Treg dominance.

Science.gov (United States)

Liu, Yun; She, Weimin; Wang, Fuping; Li, Jing; Wang, Jiyao; Jiang, Wei

2014-12-01

This study was designed to discuss the effects of 3, 3'-diindolylmethane (DIM) on methionine-choline-deficient (MCD)-diet induced mouse nonalcoholic steatohepatitis (NASH) and the potential mechanisms. NASH mice were administrated with or without DIM at different concentrations for 8 weeks. Both the in-vivo and in-vitro effects of DIM on Treg/Th17 imbalance during NASH progression were analyzed. The in-vivo blocking of CD25 or IL-17 was performed to respectively deplete respective function of Treg or Th17 subset. Besides, with the assistance of AhR antagonist CH223191 and anti-TLR4 neutralizing antibody, we designed the in-vitro DIM-incubation experiments to discuss the roles of aryl hydrocarbon receptor (AhR) (CYP1A1, CYP1B1) and toll-like receptor 4 (TLR4) on DIM's effects when shifting Treg/Th17 imbalance. Notably, in NASH mouse models, DIM alleviated hepatic steatosis and inflammation, and shifted the Treg/Th17 imbalance from MCD diet-induced Th17 dominance to Treg dominance. In-vitro, DIM not only significantly up-regulated the mRNAs of Foxp3 (Treg-specific) in purified spleen CD4(+) T cells, but also enhanced the immunosuppressive function of these Treg cells. Besides, DIM significantly up-regulated the proteins of CYP1A1 and CYP1B1 whereas down-regulated those of TLR4 on CD4(+) T cells from MCD-diet mice. Moreover, blocking AhR attenuated while blocking TLR4 enhanced the effects of DIM when regulating Treg/Th17 imbalance. Conclusively, DIM could be used as a potential therapeutic candidate to treat NASH based on its dramatic induction of Treg dominance to alleviate intra-hepatic inflammation, suggesting us a clue that the dietary cruciferous vegetables (containing abundant DIM) might exist as a protective factor for patients with NASH-related liver diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD.

Science.gov (United States)

Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A; Kleiner, David; Brunt, Elizabeth M; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James; Loomba, Rohit

2015-07-01

Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m(2), respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75-0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with

Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence.

Science.gov (United States)

Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L; Embrey, Kevin J; Golovanov, Alexander P

2016-01-22

The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly (15)N-labeled Ras as well as [(13)C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparison between 67-gallium citrate of exametazine-T-99m labelled leucocites and the DTPA-indio-111 labelled G immunoglobuline in the diagnosis of bone and articular infections; Comparacion del citrato de galio-67 de los leucocitos marcados con exametazina-tecnecio-99m y de la inmunoglobulina G marcada con DTPA-indio-111 en el diagnostico de infecciones oseas y articulares

Energy Technology Data Exchange (ETDEWEB)

Ramos, Paulo Alberto de Lima [Departamento de Ciencias Basicas da Saude. Universidade Federal da Paraiba. Campina Grande (Brazil); Martin-Comin, Josep; Roca, Manel; Ricart, Ivone; Castell, Manuel; Mora, Jaume; Puchal, Rafael; Ramos, Miguel [Servicio de Medicina Nuclear, Hospital Princeps d' Espanya. Universidad de Barcelona. Feixa Llarga s/n, 08907. Barcelona (Spain)

2000-01-01

The aim of this study was to compare the ability of 67-Gallium citrate (67Ga), 99m-Tc labelled leucocytes (99mTc-WBC) and 111-In-labelled immunoglobulin G (111In-IgG) scintigraphy in bone and joint infections diagnosis. Fifty-six patients were studied. For all patients a bone scan using 99mTc-MDP was indicated. The patients were randomized allocated for 67Ga (Group 1 - 22 patients) or simultaneous administration 99mTc-labelled leucocytes and 111In-IgG.(Group 2 - 34 patients) study. For the groups 1 and 2 were confirmed respectively 12/26 y 11/34 septic lesions. The 67Ga scintigraphy showed 6 true-positive, 9 true-negative, 5 false-positive and 6 false-negative. With 99mTc-WBC, the respective values were 8, 18, 5 and 3. With 111In-IgG, the figures were 7, 17, 6 and 4, respectively. The sensitivity, specificity and accuracy were 50%, 64,3% and 57,7% respectively for the 67Ga, 72,7%, 78,2% and 76,4% respectively for 99mTc-WBC and 63,6%, 73,9% and 70,6% respectively for 111In-IgG. In this study, the labelled leucocytes scintigraphy showed more accurate than 67Ga and 111In-IgG scans for the diagnosis of bone and joint infections. However, the obtained results were less reliable for the diagnosis of occult sepsis in the patients with joint prosthesis (Au)

Nash was a first to axiomatize expected utility

NARCIS (Netherlands)

H. Bleichrodt (Han); C. Li (Chen); I. Moscati (Ivan); P.P. Wakker (Peter)

2016-01-01

textabstractNash is famous for many inventions, but it is less known that he, simultaneously with Marschak, also was the first to axiomatize expected utility for risk. In particular, these authors were the first to state the independence condition, a condition that should have been but was not

Suppressive effects of coffee on the SOS responses induced by UV and chemical mutagens

International Nuclear Information System (INIS)

Obana, Hirotaka; Nakamura, Sei-ichi; Tanaka, Ryou-ichi

1986-01-01

SOS-inducing activity of UV or chemical mutagens was strongly suppressed by instant coffee in Salmonella typhimurium TA1535/pSK1002. As decaffeinated instant coffee showed a similarly strong suppressive effect, it would seem that caffeine, a known inhibitor of SOS responses, is not responsible for the effect observed. The suppression was also shown by freshly brewed coffee extracts. However, the suppression was absent in green coffee-bean extracts. These results suggest that coffee contains some substance(s) which, apart from caffeine, suppresses SOS-inducing activity of UV or chemical mutagens and that the suppressive substance(s) are produced by roasting coffee beans. (Auth.)

Liver transplantation for NASH cirrhosis is not performed at the expense of major post-operative morbidity

NARCIS (Netherlands)

van den Berg, Eline H.; Douwes, Rianne M.; de Meijer, Vincent E.; Schreuder, Tim C. M. A.; Blokzijl, Hans

Background: Non-alcoholic steatohepatitis (NASH) is an emerging indication for liver transplantation (LT) and coexists with multiple comorbidities. Obese and cirrhotic patients experience more perioperative complications. Limited data exist about short-term complications after LT for NASH cirrhosis.

The role of Tc-99m polyclonal human immunoglobulin G scintigraphy in Graves' ophthalmopathy

International Nuclear Information System (INIS)

Ortapamuk, H.; Hosal, B.; Naldoken, S.

2002-01-01

The aim of this study was to clarify whether Tc-99m HIG (Polyclonal Human Immunoglobulin G) can image and determine the severity of orbital involvement in patients with Graves' ophthalmopathy. Twenty-six patients between 19 and 56 years old with Graves' ophthalmopathy were examined. All patients received approximately 370 MBq Tc-99m HIG by intravenous (i.v.) injection. Planar and SPECT examination were performed 4 hours after the injection. Visual and semiquantitative evaluations were performed for both orbits by two independent observers. Clinically active ophthalmopathy patients had noticeably increased orbital accumulation of Tc-99m HIG. In patients with inactive disease, and 14 of 19 had no uptake, whereas 5 patients had orbital radioactivity accumulation. The duration of Graves' ophthalmopathy did not correlate with the presence of active ophthalmopathy and Tc-99m HIG grade. There was no correlation between clinical classification and clinical activity (r=278). There was a good correlation between clinical activity and the radioactivity grade with r=0.666 (p=0.01). The clinical classification closely correlated with Tc-99m HIG grade (r=0.423, p=0.05) Tc-99m HIG scan can clearly identified clinically active patients, and subclinical inflammation can be shown by this scintigraphic evaluation. The current preliminary results suggested that Tc-99m HIG SPECT might be useful for the assessment of disease activity in Graves' ophthalmopathy. (author)

DSS colitis promotes tumorigenesis and fibrogenesis in a choline-deficient high-fat diet-induced NASH mouse model.

Science.gov (United States)

Achiwa, Koichi; Ishigami, Masatoshi; Ishizu, Yoji; Kuzuya, Teiji; Honda, Takashi; Hayashi, Kazuhiko; Hirooka, Yoshiki; Katano, Yoshiaki; Goto, Hidemi

2016-01-29

Nonalcoholic steatohepatitis (NASH) patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Several lines of evidence indicate that accumulation of lipopolysaccharide (LPS) and disruption of gut microbiota play contributory roles in HCC. Moreover, in a dextran sodium sulfate (DSS)-induced colitis model in mice, a high-fat diet increases portal LPS level and promotes hepatic inflammation and fibrosis. However, this diet-induced NASH model requires at least 50 weeks for carcinogenesis. In this study, we sought to determine whether increased intestinal permeability would aggravate liver inflammation and fibrosis and accelerate tumorigenesis in a diet-induced NASH model. Mice were fed a choline-deficient high-fat (CDHF) diet for 4 or 12 weeks. The DSS group was fed CDHF and intermittently received 1% DSS in the drinking water. Exposure to DSS promoted mucosal changes such as crypt loss and increased the number of inflammatory cells in the colon. In the DSS group, portal LPS levels were elevated at 4 weeks, and the proportions of Clostridium cluster XI in the fecal microbiota were elevated. In addition, levels of serum transaminase, number of lobular inflammatory cells, F4/80 staining-positive area, and levels of inflammatory cytokines were all elevated in the DSS group. Liver histology in the DSS group revealed severe fibrosis at 12 weeks. Liver tumors were detected in the DSS group at 12 weeks, but not in the other groups. Thus, DSS administration promoted liver tumors in a CDHF diet-induced NASH mouse over the short term, suggesting that the induction of intestinal inflammation and gut disruption of microbiota in NASH promote hepatic tumorigenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Viral and cellular SOS-regulated motor proteins: dsDNA translocation mechanisms with divergent functions.

Science.gov (United States)

Wolfe, Annie; Phipps, Kara; Weitao, Tao

2014-01-01

DNA damage attacks on bacterial cells have been known to activate the SOS response, a transcriptional response affecting chromosome replication, DNA recombination and repair, cell division and prophage induction. All these functions require double-stranded (ds) DNA translocation by ASCE hexameric motors. This review seeks to delineate the structural and functional characteristics of the SOS response and the SOS-regulated DNA translocases FtsK and RuvB with the phi29 bacteriophage packaging motor gp16 ATPase as a prototype to study bacterial motors. While gp16 ATPase, cellular FtsK and RuvB are similarly comprised of hexameric rings encircling dsDNA and functioning as ATP-driven DNA translocases, they utilize different mechanisms to accomplish separate functions, suggesting a convergent evolution of these motors. The gp16 ATPase and FtsK use a novel revolution mechanism, generating a power stroke between subunits through an entropy-DNA affinity switch and pushing dsDNA inward without rotation of DNA and the motor, whereas RuvB seems to employ a rotation mechanism that remains to be further characterized. While FtsK and RuvB perform essential tasks during the SOS response, their roles may be far more significant as SOS response is involved in antibiotic-inducible bacterial vesiculation and biofilm formation as well as the perspective of the bacteria-cancer evolutionary interaction.

Comparison between 67-gallium citrate of exametazine-T-99m labelled leucocites and the DTPA-indio-111 labelled G immunoglobuline in the diagnosis of bone and articular infections

International Nuclear Information System (INIS)

Ramos, Paulo Alberto de Lima; Martin-Comin, Josep; Roca, Manel; Ricart, Ivone; Castell, Manuel; Mora, Jaume; Puchal, Rafael; Ramos, Miguel

2000-01-01

The aim of this study was to compare the ability of 67-Gallium citrate (67Ga), 99m-Tc labelled leucocytes (99mTc-WBC) and 111-In-labelled immunoglobulin G (111In-IgG) scintigraphy in bone and joint infections diagnosis. Fifty-six patients were studied. For all patients a bone scan using 99mTc-MDP was indicated. The patients were randomized allocated for 67Ga (Group 1 - 22 patients) or simultaneous administration 99mTc-labelled leucocytes and 111In-IgG.(Group 2 - 34 patients) study. For the groups 1 and 2 were confirmed respectively 12/26 y 11/34 septic lesions. The 67Ga scintigraphy showed 6 true-positive, 9 true-negative, 5 false-positive and 6 false-negative. With 99mTc-WBC, the respective values were 8, 18, 5 and 3. With 111In-IgG, the figures were 7, 17, 6 and 4, respectively. The sensitivity, specificity and accuracy were 50%, 64,3% and 57,7% respectively for the 67Ga, 72,7%, 78,2% and 76,4% respectively for 99mTc-WBC and 63,6%, 73,9% and 70,6% respectively for 111In-IgG. In this study, the labelled leucocytes scintigraphy showed more accurate than 67Ga and 111In-IgG scans for the diagnosis of bone and joint infections. However, the obtained results were less reliable for the diagnosis of occult sepsis in the patients with joint prosthesis (Au)

Plasminogen activator inhibitor type 1 serum levels and 4G/5G gene polymorphism in morbidly obese Hispanic patients with non-alcoholic fatty liver disease.

Science.gov (United States)

Espino, Alberto; Villagrán, Andrea; Vollrath, Valeska; Hanckes, Paulina; Salas, Roberto; Farah, Andrea; Solís, Nancy; Pizarro, Margarita; Escalona, Alex; Boza, Camilo; Pérez, Gustavo; Carrasco, Gonzalo; Padilla, Oslando; Miquel, Juan Francisco; Nervi, Flavio; Chavez-Tapia, Norberto C; Arab, Juan Pablo; Alvarez-Lobos, Manuel; Arrese, Marco; Riquelme, Arnoldo

2011-01-01

The plasminogen activator inhibitor type-1 (PAI-1) has been implicated in the regulation of fibrinolysis and extracellular matrix components. The single base pair guanine insertion/deletion polymorphism (4G/5G) within the promoter region of the PAI-1 gene influences PAI-1 synthesis and may modulate hepatic fibrogenesis. To evaluate the influence of PAI-1 serum levels and 4G/5G polymorphism on the risk of liver fibrosis associated to non-alcoholic fatty liver disease (NAFLD) in morbidly obese patients. Case-control study of 50 obese patients undergoing bariatric surgery and 71 non-obese subjects matched by age and sex. Anthropometric and biochemical measurements were performed, including PAI-1 serum levels. Genomic DNA was obtained to assess the presence of 4G/5G polymorphism. BMI, insulinemia, triglycerides, HOMA-IR, hypertension and diabetes were significantly higher in obese patients compared to control subjects. PAI-1 serum levels observed in obese patients were significantly lower (10.63 ± 4.82) compared to controls (14.26 ± 11.4; p 5G promoter genotypes frequencies (p = 0.12). No differences were observed in PAI-1 plasma levels among obese patients with liver fibrosis (10.64 ± 4.35) compared to patients without liver fibrosis (10.61 ± 5.2; p = 0.985). PAI-1 4G/5G promoter genotypes frequencies were similar in patients with or without liver fibrosis associated to NASH (p = 0.6). Morbidly obese patients had significantly lower PAI-1 serum levels with similar PAI-1 4G/5G genotypes frequencies compared to non-obese subjects. The frequency of 4G/5G genotypes in Chilean Hispanic healthy subjects was similar to that described in other populations. No association was found between PAI-1 serum levels or 4G/5G genotype with liver fibrosis in obese patients.

Detection of early psychotic symptoms: Validation of the Spanish version of the "Symptom Onset in Schizophrenia (SOS) inventory".

Science.gov (United States)

Mezquida, Gisela; Cabrera, Bibiana; Martínez-Arán, Anabel; Vieta, Eduard; Bernardo, Miguel

2018-03-01

The period of subclinical signs that precedes the onset of psychosis is referred to as the prodrome or high-risk mental state. The "Symptom Onset in Schizophrenia (SOS) inventory" is an instrument to characterize and date the initial symptoms of a psychotic illness. The present study aims to provide reliability and validity data for clinical and research use of the Spanish version of the SOS. Thirty-six participants with a first-episode of psychosis meeting DSM-IV criteria for schizophrenia/schizoaffective/schizophreniform disorder were administered the translated SOS and other clinical assessments. The internal validity, intrarater and interrater reliability were studied. We found strong interrater reliability. To detect the presence/absence of prodromal symptoms, Kappa coefficients ranged between 0.8 and 0.7. Similarly, the raters obtained an excellent level of agreement regarding the onset of each symptom and the duration of symptoms until first treatment (intraclass correlation coefficients between 0.9 and 1.0). Cronbach's alpha was 0.9-1.0 for all the items. The interrater reliability and concurrent validity were also excellent in both cases. This study provides robust psychometric properties of the Spanish version of the SOS. The translated version is adequate in terms of good internal validity, intrarater and interrater reliability, and is as time-efficient as the original version. Copyright © 2017 Elsevier B.V. All rights reserved.

Sensor Data from the NERACOOS SOS Server, 2000-present

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Northeastern Regional Association of Coastal Ocean Observing Systems (NERACOOS) Sensor Observation Service (SOS) The OCEANS IE -- formally approved as an OGC...

A freeze dried kit formulation for the preparation of 99m Tc labelled human polyclonal IgG for the detection of infection and inflammation

International Nuclear Information System (INIS)

Pedraza L, M.

1996-01-01

A freeze dried kit formulation for the preparation of 99m Tc-labelled human polyclonal IgG for the detection of infection and inflammation employing direct methods for protein labeling was developed. The method comprises reduction of intrinsic disulphide bridges within the antibody molecule by the use of the reductant 2-mercaptoethanol. Following a subsequent purification, the resulting reduced antibody is labeled via Sn 2+ reduction of pertechnetate in the presence of a weak competing ligand ethane-1-hydroxy-1,1-diphosphonate (EHDP). High labeling efficiencies (>90%) were obtained with high in vitro stability and without effect upon antibody immunoreactivity. Methods of analysis were also established permitting identification of radiochemical impurities which may be present in radiopharmaceutical solution. 99m Tc-polyclonal IgG prepared by the kit method was evaluated for scintigraphic localization of inflammatory lesions and abscesses in rabbits. Data demonstrated that the 99m Tc-polyclonal IgG after kit-reconstitution shows excellent stability and is an effective imaging agent of infection and/or inflammation. (Author)

Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios

DEFF Research Database (Denmark)

Jørgensen, Henrik L; Kusk, Philip; Madsen, Bente Elmfelt

2004-01-01

66 women with lower forearm fracture, 41 women with hip fracture, and 206 age-matched controls. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel as well as bone mineral density (BMD) measured by DXA at the distal forearm. S-OPG was measured by ELISA. The A......163G genotypes were determined by PCR-RFLP analysis. S-OPG levels correlated positively with age ( r = 0.45; P heel BUA ( r = -0.23; P heel SOS ( r = -0.22; P ...-OPG to the lowest, the odds ratio for osteoporotic fracture was 2.5 (95% CI, 1.3-4.7; P = 0.006). The G allele of the A163G was associated with significantly lower t-scores of both lower forearm BMD, heel BUA, and heel SOS as well as being significantly more frequent in the fracture patients compared...

MicroRNA Expression Relating to Dietary-Induced Liver Steatosis and NASH

Directory of Open Access Journals (Sweden)

Aida Zarfeshani

2015-11-01

Full Text Available Health issues associated with excessive caloric intake and sedentary lifestyle are driving a modern “epidemic” of liver disease. Initially presenting in the clinic as an excessive accumulation of fat within hepatocyte cells (steatosis, the progression to more severe non-alcoholic steatohepatitis (NASH in which liver damage and inflammation are overt features, is becoming increasingly common. Often developing as a sequela of obesity, non-alcoholic fatty liver disease (NAFLD arises in almost one-third of people initially carrying excess hepatic fat and is likely the result of the liver’s limited capacity to cope with the modern-day levels of dietary fatty acids circulating in the blood. While routine imaging can readily assess the presence and level of “extra-hepatic fat”, a proper diagnosis of disease progression to NASH is currently only possible by liver biopsy. A general reluctance to undergo such screening means that the prevalence of NASH is likely to be under reported and, thus, risk assessment for future metabolic syndrome (MetS markedly compromised. The seemingly inevitable progression to overt insulin resistance that characterizes MetS may in part be the consequence of the body’s attempt to cope with NAFLD by driving systemic insulin sensitivity and, thus, fatty acid breakdown. The potential significance of miRNAs in both physiological homeostasis and pathogenesis is increasingly appreciated and in the liver may contribute specifically to the regulation of lipid pathways and NAFLD progression. As such, they may have utility as molecular indicators for the accurate profiling of both initial risk and disease progression from simple steatosis to NASH, and further to fibrosis/cirrhosis.

Physical modeling of SOS P channel MOSFET and comparison with bulk devices

International Nuclear Information System (INIS)

Merckel, G.; Gris, Y.

1976-01-01

The main technological steps applied to P channel MOSFET's on SOS are recalled. A large-signal model derived from a physical analysis is presented. Gate-source and gate-drain capacitors have been linearized versus drain voltage. Due to low injection, the only diffusion capacitance of the source-substrate forward biased diode, and the depletion capacitance of the drain-substrate reverse biased diode were taken into account. Some typical parameters measured on SOS and bulk devices are given [fr

99mTc gel generators based on zirconium molybdate-99Mo: III: Influence of preparatory conditions of zirconium molybdate-99Mo gel on generator performance

International Nuclear Information System (INIS)

Saraswathy, P.; Sarkar, S.K.; Arjun, G.; Ramamoorthy, N.; Nandy, S.K.

2004-01-01

The effect of subtle variations on zirconium molybdate- 99 Mo gel preparatory conditions, such as stoichiometry of reactants, pH of gel formation, conditioning of gel granules etc., prior to elution were investigated primarily to arrive at the conditions resulting in high 99m Tc release and minimal 99 Mo breakthrough upon elution with normal saline. Zirconium molybdate- 99 Mo gels were prepared by reacting solutions of Zr and Mo in mole ratios of 0.75-1.5. Both water and normal saline were used for gel disintegration, and the release of 99m Tc and 99 Mo from gel columns into eluates was compared. Sharper elution profile of 99m Tc, but with significantly higher 99 Mo breakthrough (5-8 times), was obtained when water alone was used for disintegration and elution, in comparison to when saline was used. Gels exhibiting optimum characteristics were found to be formed at a pH of 4-5 by reacting [Zr]: [Mo] in the mole ratio of 1.25: 1 and after drying, the product was dispersed into granules by disintegration with normal saline. 99m Tc elution efficiency was found to be ∝ 75% and 99 Mo breakthrough ∝ 0.05%. The elution profile was sharp when a 6 g gel column coupled to a 2 g acidic alumina column (to trap 99 Mo) was eluted with 6-9 ml normal saline. Generators containing upto 23 GBq 99 Mo were prepared, eluted extensively without changing the alumina column and found to provide pertechnetate of good quality, commensurate with hospital radiopharmacy requirements. (orig.)

Induction of sos response in Escherichia Coli cells by gamma rays

International Nuclear Information System (INIS)

Fuentes Lorenzo, J.L.; Padron Soler, E.; Martin Hernandez, G.; Perez Tamayo, N.; del Sol Abascal, E.R.; Almeida Varela, E.

1996-01-01

The kinetics of sos response induction in Escherichia Coli cells was studied by means of the gene fusion SfiA:LacZ. In these cells, the specific beta galactosidase activity and the cellular growth rate showed an exponential behaviour. The sensitivity of the GC 2181 starin to gamma irradiation is equal to Do -1= 0.00088/Gy. The beta galactosidase activity

Kinetic and dose dependencies of the SOS-induction in E.coli K-12 (uvrA) cells exposed to different UV doses

International Nuclear Information System (INIS)

Komova, O.V.; Kandiano, E.S.; Malavina, G.; )

2000-01-01

Kinetic and dose dependencies of the SOS-induction in E. coli (uvrA) cells exposed to UV light were investigated. below 2 J/m 2 the rate of the SOS-induction increased with dose. Maximal level of the SOS-response was proportional to the UV dose. Pyrimidine dimers were necessary for the induction. In the dose range 2-10 J/m 2 the rate of SOS-induction decreased with dose. Dose-maximum response curve was non-linear. Pyrimidine dimers were not required for the induction. nature of the molecular events leading to the SOS-induction at low and high doses was discussed [ru

Chemical trapping and characterization of small oxoacids of sulfur (SOS) generated in aqueous oxidations of H2S.

Science.gov (United States)

Kumar, Murugaeson R; Farmer, Patrick J

2018-04-01

Small oxoacids of sulfur (SOS) are elusive molecules like sulfenic acid, HSOH, and sulfinic acid, HS(O)OH, generated during the oxidation of hydrogen sulfide, H 2 S, in aqueous solution. Unlike their alkyl homologs, there is a little data on their generation and speciation during H 2 S oxidation. These SOS may exhibit both nucleophilic and electrophilic reactivity, which we attribute to interconversion between S(II) and S(IV) tautomers. We find that SOS may be trapped in situ by derivatization with nucleophilic and electrophilic trapping agents and then characterized by high resolution LC MS. In this report, we compare SOS formation from H 2 S oxidation by a variety of biologically relevant oxidants. These SOS appear relatively long lived in aqueous solution, and thus may be involved in the observed physiological effects of H 2 S. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

[Effects and mechanisms of the inflammatory reaction related to NASH and induced by activation of the cholinergic anti-inflammatory pathway].

Science.gov (United States)

Zhou, Zhou; Chen, Xiaomei; Li, Fuqiang; Tang, Cuilan

2015-01-01

To investigate the effects and mechanisms of the inflammatory reaction related to nonalcoholic steatohepatitis (NASH) and induced by activation of the cholinergic anti-inflammatory pathway. A mouse model of NASH was established by feeding a high-fat and high-sugar diet.Activation of the cholinergic anti-inflammatory pathway was achieved by nicotine administration to the NASH modeled mice and normal controls. Liver biopsies were taken and the concentrations of cytokines were measured. Isolated liver primary Kupffer cells and RAw264.7 cells were cultured, pre-treated or not with lipopolysaccharide (LPS) and exposed to nicotine, after which the supernatant concentrations of IL-6 and TNFa were determined by ELISA. The protein expression levels of phosphorylated (p)-NF-kB and I k B were detected in primary cultured Kupffer cells by western blotting. The mouse model of NASH was successfully established, as evidenced by findings from liver biopsy and serum liver function tests. The degree of liver inflammation in the NASH mice decreased after nicotine administration, and the level of serum TNFa also significantly decreased. The levels of serum TNFa were 21.95+/-0.8 pg/mL in nicotine-treated mice and 38.07+/-1.7 pg/mL in the non-nicotine-treated NASH mice (P less than 0.05). The nicotine treatment also significantly reduced the concentration of TNFa in the culture supernatants of Kupffer cells after LPS stimulation; moreover, the supernatant level of TNFa decreased significantly after the nicotine treatment (Pless than 0.05). LPS stimulation of the RAw264.7 cells led to an increased level ofp-NF-kB and a reduced level ofI-kB, suggesting that the NF-kB pathway had been activated; different doses of nicotine pre-treatment led to down-regulation of the p-NF-kB level and up-regulation of the I-kB level, both in dose-dependent manners. Activating the cholinergic anti-inflammatory pathway inhibits the NASH-related inflammatory reaction, and the mechanism for this inhibition

Nash equilibrium strategy in the deregulated power industry and comparing its lost welfare with Iran wholesale electricity market

Science.gov (United States)

Mousavi, Seyed Hosein; Nazemi, Ali; Hafezalkotob, Ashkan

2016-09-01

With the increasing use of different types of auctions in market designing, modeling of participants' behaviors to evaluate the market structure is one of the main discussions in the studies related to the deregulated power industries. In this article, we apply an approach of the optimal bidding behavior to the Iran wholesale electricity market as a restructured electric power industry and model how the participants of the market bid in the spot electricity market. The problem is formulated analytically using the Nash equilibrium concept composed of large numbers of players having discrete and very large strategy spaces. Then, we compute and draw supply curve of the competitive market in which all generators' proposed prices are equal to their marginal costs and supply curve of the real market in which the pricing mechanism is pay-as-bid. We finally calculate the lost welfare or inefficiency of the Nash equilibrium and the real market by comparing their supply curves with the competitive curve. We examine 3 cases on November 24 (2 cases) and July 24 (1 case), 2012. It is observed that in the Nash equilibrium on November 24 and demand of 23,487 MW, there are 212 allowed plants for the first case (plants are allowed to choose any quantity of generation except one of them that should be equal to maximum Power) and the economic efficiency or social welfare of Nash equilibrium is 2.77 times as much as the real market. In addition, there are 184 allowed plants for the second case (plants should offer their maximum power with different prices) and the efficiency or social welfare of Nash equilibrium is 3.6 times as much as the real market. On July 24 and demand of 42,421 MW, all 370 plants should generate maximum energy due to the high electricity demand that the economic efficiency or social welfare of the Nash equilibrium is about 2 times as much as the real market.

Association between GRB2/Sos and insulin receptor substrate 1 is not sufficient for activation of extracellular signal-regulated kinases by interleukin-4: implications for Ras activation by insulin.

Science.gov (United States)

Pruett, W; Yuan, Y; Rose, E; Batzer, A G; Harada, N; Skolnik, E Y

1995-03-01

Insulin receptor substrate 1 (IRS-1) mediates the activation of a variety of signaling pathways by the insulin and insulin-like growth factor 1 receptors by serving as a docking protein for signaling molecules with SH2 domains. We and others have shown that in response to insulin stimulation IRS-1 binds GRB2/Sos and have proposed that this interaction is important in mediating Ras activation by the insulin receptor. Recently, it has been shown that the interleukin (IL)-4 receptor also phosphorylates IRS-1 and an IRS-1-related molecule, 4PS. Unlike insulin, however, IL-4 fails to activate Ras, extracellular signal-regulated kinases (ERKs), or mitogen-activated protein kinases. We have reconstituted the IL-4 receptor into an insulin-responsive L6 myoblast cell line and have shown that IRS-1 is tyrosine phosphorylated to similar degrees in response to insulin and IL-4 stimulation in this cell line. In agreement with previous findings, IL-4 failed to activate the ERKs in this cell line or to stimulate DNA synthesis, whereas the same responses were activated by insulin. Surprisingly, IL-4's failure to activate ERKs was not due to a failure to stimulate the association of tyrosine-phosphorylated IRS-1 with GRB2/Sos; the amounts of GRB2/Sos associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. Moreover, the amounts of phosphatidylinositol 3-kinase activity associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. In contrast to insulin, however, IL-4 failed to induce tyrosine phosphorylation of Shc or association of Shc with GRB2. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Previous studies have indicated that activation of ERks in this cell line is dependent upon Ras since a dominant-negative Ras (Asn-17) blocks ERK activation by insulin. Our findings, taken in the context

On pure-strategy Nash equilibria in price-quantity games

NARCIS (Netherlands)

Bos, I.; Vermeulen, A.J.

2015-01-01

This paper examines the existence and characteristics of pure-strategy Nash equilibria in oligopoly models in which firms set both prices and quantities. Existence is proved for a broad and natural class of price-quantity games. With differentiated products, the equilibrium outcome is similar to

On the Open-Loop Nash Equilibrium in LQ-Games

NARCIS (Netherlands)

Engwerda, J.C.

1996-01-01

In this paper we consider open-loop Nash equilibria of the linear-quadratic differential game.As well the finite-planning-horizon, the infinite-planning horizon as convergence properties of the finite-planning-horizon equilibrium if the planning horizon is extended to infinity are studied.Particular

Characterization of the Burkholderia thailandensis SOS response by using whole-transcriptome shotgun sequencing.

Science.gov (United States)

Ulrich, Ricky L; Deshazer, David; Kenny, Tara A; Ulrich, Melanie P; Moravusova, Anna; Opperman, Timothy; Bavari, Sina; Bowlin, Terry L; Moir, Donald T; Panchal, Rekha G

2013-10-01

The bacterial SOS response is a well-characterized regulatory network encoded by most prokaryotic bacterial species and is involved in DNA repair. In addition to nucleic acid repair, the SOS response is involved in pathogenicity, stress-induced mutagenesis, and the emergence and dissemination of antibiotic resistance. Using high-throughput sequencing technology (SOLiD RNA-Seq), we analyzed the Burkholderia thailandensis global SOS response to the fluoroquinolone antibiotic, ciprofloxacin (CIP), and the DNA-damaging chemical, mitomycin C (MMC). We demonstrate that a B. thailandensis recA mutant (RU0643) is ∼4-fold more sensitive to CIP in contrast to the parental strain B. thailandensis DW503. Our RNA-Seq results show that CIP and MMC treatment (P SOS response were induced and include lexA, uvrA, dnaE, dinB, recX, and recA. At the genome-wide level, we found an overall decrease in gene expression, especially for genes involved in amino acid and carbohydrate transport and metabolism, following both CIP and MMC exposure. Interestingly, we observed the upregulation of several genes involved in bacterial motility and enhanced transcription of a B. thailandensis genomic island encoding a Siphoviridae bacteriophage designated E264. Using B. thailandensis plaque assays and PCR with B. mallei ATCC 23344 as the host, we demonstrate that CIP and MMC exposure in B. thailandensis DW503 induces the transcription and translation of viable bacteriophage in a RecA-dependent manner. This is the first report of the SOS response in Burkholderia spp. to DNA-damaging agents. We have identified both common and unique adaptive responses of B. thailandensis to chemical stress and DNA damage.

Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study.

Science.gov (United States)

Duarte, S M B; Stefano, J T; Miele, L; Ponziani, F R; Souza-Basqueira, M; Okada, L S R R; de Barros Costa, F G; Toda, K; Mazo, D F C; Sabino, E C; Carrilho, F J; Gasbarrini, A; Oliveira, C P

2018-04-01

The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences. We performed a cross-sectional pilot study comprising biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software. Macronutrient consumption was analyzed by a 7-day food record. Liver fibrosis ≥ F2 was associated with increased abundance of Lactobacilli (p = 0.0007). NASH patients showed differences in Faecalibacterium, Ruminococcus, Lactobacillus and Bifidobacterium abundance compared with the control group. Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004), obese NASH patients were enriched in Lactobacilli (p = 0.002), and overweight NASH patients had reduced Bifidobacterium (p = 0.018). Moreover, lean NASH patients showed a deficiency in Lactobacillus compared with overweight and obese NASH patients. This group also appeared similar to the control group with regard to gut microbiome alpha diversity. Although there were qualitative differences between lean NASH and overweight/obese NASH, they were not statistically significant (p = 0.618). The study limitations included a small sample size, a food questionnaire that collected only qualitative and semi-quantitative data, and variations in group gender composition that may influence differences in FXR signaling, bile acids metabolism and the composition of gut microbiota. Our preliminary finding of a different pathogenetic process in lean NASH patients needs to be confirmed by larger studies, including those with patient populations stratified by sex and dietary habits. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the

Evaluation of (99m)Tc-HYNIC-TMTP1 as a tumor-homing imaging agent targeting metastasis with SPECT.

Science.gov (United States)

Li, Fei; Cheng, Teng; Dong, Qingjian; Wei, Rui; Zhang, Zhenzhong; Luo, Danfeng; Ma, Xiangyi; Wang, Shixuan; Gao, Qinglei; Ma, Ding; Zhu, Xiaohua; Xi, Ling

2015-03-01

TMTP1 (NVVRQ) is a novel tumor-homing peptide, which specifically targets tumor metastases, even at the early stage of occult metastasis foci. Fusing TMTP1 to therapeutic peptides or proteins can increase its anti-cancer efficacy both in vivo and in vitro. Here, we labeled TMTP1 with (99m)Tc to evaluate its targeting properties in an ovarian cancer xenograft tumor mouse model and a gastric cancer xenograft mouse model. The invasion ability of SKOV3 and highly metastatic SKOV3.ip cell lines were performed by the Transwell Invasion Assays, and then Rhodamine-TMTP1 was used to detect its affinity to these two cells. Using the co-ligand ethylenediamine-N, N'-diacetic acid (EDDA) and the bifunctional chelator 6-hydrazinonicotinic acid (HYNIC), the TMTP1 peptide was labeled with (99m)Tc. A cell-binding assay was performed by incubating cancer cells with (99m)Tc-HYNIC-TMTP1 with or without an excess dose of cold HYNIC-TMTP1. To evaluate the probe in vivo, nude mice bearing SKOV3, SKOV3.ip and MNK-45 tumor cells were established and subjected to SPECT imaging after injection with (99m)Tc-HYNIC-TMTP1. Ex vivo γ-counting of dissected tissues from the mice was used to evaluate its biodistribution. (99m)Tc-HYNIC-TMTP1 was successfully synthesized. The radiotracer also exhibited high hydrophilicity and excellent stability in vitro and in vivo. It has strong affinity to highly metastatic cancer cell lines but not to poorly metastatic cell lines. After mice were injected with (99m)Tc-HYNIC-TMTP1, non-invasive SPECT imaging detected SKOV3.ip and MNK-45 xenograft tumors but not SKOV3 xenograft tumors. This result can be inhibited by excess HYNIC-TMTP1. The uptake of (99m)Tc-HYNIC-TMTP1 in SKOV3.ip xenograft tumors was 0.182±0.017% ID/g at 2h p.i. with high renal uptake (74.32±15.05% ID/g at 2h p.i.). (99m)Tc-HYNIC-TMTP1 biodistribution and SPECT imaging demonstrated its ability to target highly metastatic tumors. Therefore, metastasis can be non-invasively investigated by SPECT

Assessment of Some Adipo cytokines Levels In Serum of Egyptian Patients Suffering From Non-Alcoholic Steatohepatitis (NASH)

International Nuclear Information System (INIS)

Mohammed, A.A.

2011-01-01

In the present study, thirty five patients with biopsy proven NASH and twenty age and sex matched healthy individuals were enrolled. Serum adiponectin, ghrelin, TNF-α and leptin levels were estimated in the serum of NASH patients and control subjects. Also, fasting insulin and blood glucose levels were measured and insulin resistance (IR) were calculated. In addition, liver function enzymes (AST, ALT), total cholesterol and triglycerides were measured, and body mass index (BMI) was calculated. The results showed significant decrease in adiponectin and ghrelin levels and significant increase in TNF-α and leptin levels in NASH group as compared to controls. Ten patients were diabetic and seven patients had BMI > 30 kg/m 2 . Also, significant positive relationship was recorded between adiponectin and ghrelin and AST/ALT ratio in the NASH group, and significant negative relationship between them and BMI and HOMA-IR

Quantum mechanics gives stability to a Nash equilibrium

International Nuclear Information System (INIS)

Iqbal, A.; Toor, A.H.

2002-01-01

We consider a slightly modified version of the rock-scissors-paper (RSP) game from the point of view of evolutionary stability. In its classical version the game has a mixed Nash equilibrium (NE) not stable against mutants appearing in small numbers. We find a quantized version of the RSP game for which the classical mixed NE becomes stable

[99mTc]Demotensin 5 and 6 in the NTS1-R-targeted imaging of tumours: synthesis and preclinical results

International Nuclear Information System (INIS)

Maina, Theodosia; Nikolopoulou, Anastasia; Stathopoulou, Eleni; Nock, Berthold A.; Galanis, Athanassios S.; Cordopatis, Paul

2007-01-01

The aim of this study was to evaluate the applicability of [ 99m Tc]Demotensin 5 and 6 ([ 99m Tc- N 0 4 ,(β)Ala 7 ,Dab 9 ,X 12 AA ]NT(7-13); X AA =Ile/5,Tle/6,NT=neurotensin) in the targeted diagnostic imaging of neurotensin subtype 1 receptor (NTS1-R)-expressing tumours. Labelling of Demotensin 5 and 6 with 99m Tc was conducted by brief incubation with 99m TcO 4 - , SnCl 2 and citrate anions in alkaline medium at ambient temperature. Affinities of conjugates for the NTS1-R were determined by competition binding experiments in WiDr cell membranes using [ 125 I-Tyr 3 ]NT as the radioligand. Saturation binding assays were conducted for [ 99m Tc/ 99g Tc]Demotensin 6 in WiDr cell membranes. Internalisation of [ 99m Tc]Demotensin 5 and 6 was studied at 37 C in WiDr cells. Biodistribution of [ 99m Tc]Demotensin 5 and 6 was performed in female Swiss nu/nu mice bearing human WiDr xenografts. Unlabelled conjugates showed a high affinity for the human NTS1-R (Demotensin 5 IC 50 =0.03±0.01 nM; Demotensin 6 IC 50 =0.08±0.02 nM), while high affinity was also exhibited by (radio)metallated [ 99m Tc/ 99g Tc]Demotensin 6 (K d =0.13±0.01 nM). [ 99m Tc]Demotensin 5 and 6 internalised rapidly and specifically in WiDr cells. After injection in WiDr tumour-bearing mice, radiopeptides, and especially the doubly stabilised [ 99m Tc]Demotensin 6, showed NTS1-R-mediated uptake in the intestines and in the implanted tumour (4.30±0.45%ID/g at 1 h post injection) and rapid renal excretion from non-target tissues into the urine. [ 99m Tc]Demotensin 6 shows a favourable preclinical profile and further testing in patients is warranted to monitor its eventual applicability as a radiotracer in the diagnostic imaging of NTS1-R-positive tumours. (orig.)

TREATABILITY TEST FOR REMOVING TECHNETIUM-99 FROM 200-ZP-1 GROUNDWATER HANFORD SITE

Energy Technology Data Exchange (ETDEWEB)

PETERSEN SW; TORTOSO AC; ELLIOTT WS; BYRNES ME

2007-11-29

The 200-ZP-1 Groundwater Operable Unit (OU) is one of two groundwater OUs located within the 200 West groundwater aggregate area of the Hanford Site. The primary risk-driving contaminants within the 200-ZP-1 OU include carbon tetrachloride and technetium-99 (Tc-99). A pump-and-treat system for this OU was initially installed in 1995 to control the 0.002 kg/m{sup 3} (2000 {micro}g/L) contour of the carbon tetrachloride plume. Carbon tetrachloride is removed from groundwater with the assistance of an air-stripping tower. Ten extraction wells and three injection wells operate at a combined rate of approximately 0.017m{sup 3}/s (17.03 L/s). In 2005, groundwater from two of the extraction wells (299-W15-765 and 299-W15-44) began to show concentrations greater than twice the maximum contaminant level (MCL) of Tc-99 (33,309 beq/m{sup 3} or 900 pCi/L). The Tc-99 groundwater concentrations from all ten of the extraction wells when mixed were more than one-half of the MCL and were slowly increasing. If concentrations continued to rise and the water remained untreated for Tc-99, there was concern that the water re-injected into the aquifer could exceed the MCL standard. Multiple treatment technologies were reviewed for selectively removing Tc-99 from the groundwater. Of the treatment technologies, only ion exchange was determined to be highly selective, commercially available, and relatively low in cost. Through research funded by the U.S. Department of Energy, the ion-exchange resin Purolite{reg_sign} A-530E was found to successfully remove Tc-99 from groundwater, even in the presence of competing anions. For this and other reasons, Purolite{reg_sign} A-530E ion exchange resin was selected for treatability testing. The treatability test required installing resin columns on the discharge lines from extraction wells 299-W15-765 and 299-W15-44. Preliminary test results have concluded that the Purolite{reg_sign} A-530E resin is effective at removing Tc-99 from groundwater to

RpoS plays a central role in the SOS induction by sub-lethal aminoglycoside concentrations in Vibrio cholerae.

Science.gov (United States)

Baharoglu, Zeynep; Krin, Evelyne; Mazel, Didier

2013-01-01

Bacteria encounter sub-inhibitory concentrations of antibiotics in various niches, where these low doses play a key role for antibiotic resistance selection. However, the physiological effects of these sub-lethal concentrations and their observed connection to the cellular mechanisms generating genetic diversification are still poorly understood. It is known that, unlike for the model bacterium Escherichia coli, sub-minimal inhibitory concentrations (sub-MIC) of aminoglycosides (AGs) induce the SOS response in Vibrio cholerae. SOS is induced upon DNA damage, and since AGs do not directly target DNA, we addressed two issues in this study: how sub-MIC AGs induce SOS in V. cholerae and why they do not do so in E. coli. We found that when bacteria are grown with tobramycin at a concentration 100-fold below the MIC, intracellular reactive oxygen species strongly increase in V. cholerae but not in E. coli. Using flow cytometry and gfp fusions with the SOS regulated promoter of intIA, we followed AG-dependent SOS induction. Testing the different mutation repair pathways, we found that over-expression of the base excision repair (BER) pathway protein MutY relieved this SOS induction in V. cholerae, suggesting a role for oxidized guanine in AG-mediated indirect DNA damage. As a corollary, we established that a BER pathway deficient E. coli strain induces SOS in response to sub-MIC AGs. We finally demonstrate that the RpoS general stress regulator prevents oxidative stress-mediated DNA damage formation in E. coli. We further show that AG-mediated SOS induction is conserved among the distantly related Gram negative pathogens Klebsiella pneumoniae and Photorhabdus luminescens, suggesting that E. coli is more of an exception than a paradigm for the physiological response to antibiotics sub-MIC.

Integral formula for elliptic SOS models with domain walls and a reflecting end

Energy Technology Data Exchange (ETDEWEB)

Lamers, Jules, E-mail: j.lamers@uu.nl

2015-12-15

In this paper we extend previous work of Galleas and the author to elliptic SOS models. We demonstrate that the dynamical reflection algebra can be exploited to obtain a functional equation characterizing the partition function of an elliptic SOS model with domain-wall boundaries and one reflecting end. Special attention is paid to the structure of the functional equation. Through this approach we find a novel multiple-integral formula for that partition function.

'99Mo/99mTc Generator Based on High Radionuclidic Pure Zirconium Molybdate Gel

International Nuclear Information System (INIS)

Amin, M.; Mostafa, M.; El-Amir, M.A.; El-Absy, M.A.; Mohamed, O.I.; Farag, A.B.

2014-01-01

99 Mo / 99 mTc radioisotope generator was prepared using in-situ precipitated zirconium molybdate chromatographic column. Zirconium molybdate gel matrix was synthesized by precipitation of neutron activation molybdenum-99 from its solution after variety purification processes to prevent contamination of the 99m Tc eluate with cross-contaminants. Greeter than 82.7 ± 0.4 % of the generated 99m Tc was immediately and reproducible eluted by passing 10 ml 0.9 % NaCl solution through the 1 g zirconium molybdate- 99 Mo column matrix at a flow rate of 0.5 ml / min and room temperature with high chemical, radionuclide ( ≥ 99.9 % 99m Tc) and radiochemical purity ( ≥ 97.7 % % as 99 mTcO 4 - ) with ph value suitable for medical uses.

Feedback nash equilibria for linear quadratic descriptor differential games

NARCIS (Netherlands)

Engwerda, J.C.; Salmah, S.

2012-01-01

In this paper, we consider the non-cooperative linear feedback Nash quadratic differential game with an infinite planning horizon for descriptor systems of index one. The performance function is assumed to be indefinite. We derive both necessary and sufficient conditions under which this game has a

On the Sensitivity Matrix of the Nash Bargaining Solution

NARCIS (Netherlands)

Engwerda, J.C.

2006-01-01

In this note we provide a characterization of a subclass of bargaining problems for which the Nash solution has the property of disagreement point monotonicity.While the original d-monotonicity axiom and its stronger notion, strong d-monotonicity, were introduced and discussed by Thomson [15], this

Feedback Nash Equilibria for Linear Quadratic Descriptor Differential Games

NARCIS (Netherlands)

Engwerda, J.C.; Salmah, Y.

2010-01-01

In this note we consider the non-cooperative linear feedback Nash quadratic differential game with an infinite planning horizon for descriptor systems of index one. The performance function is assumed to be indefinite. We derive both necessary and sufficient conditions under which this game has a

Atomic orbital-based SOS-MP2 with tensor hypercontraction. I. GPU-based tensor construction and exploiting sparsity

Energy Technology Data Exchange (ETDEWEB)

Song, Chenchen; Martínez, Todd J. [Department of Chemistry and the PULSE Institute, Stanford University, Stanford, California 94305 (United States); SLAC National Accelerator Laboratory, Menlo Park, California 94025 (United States)

2016-05-07

We present a tensor hypercontracted (THC) scaled opposite spin second order Møller-Plesset perturbation theory (SOS-MP2) method. By using THC, we reduce the formal scaling of SOS-MP2 with respect to molecular size from quartic to cubic. We achieve further efficiency by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs) to accelerate integral construction and matrix multiplication. The practical scaling of GPU-accelerated atomic orbital-based THC-SOS-MP2 calculations is found to be N{sup 2.6} for reference data sets of water clusters and alanine polypeptides containing up to 1600 basis functions. The errors in correlation energy with respect to density-fitting-SOS-MP2 are less than 0.5 kcal/mol for all systems tested (up to 162 atoms).

Atomic orbital-based SOS-MP2 with tensor hypercontraction. I. GPU-based tensor construction and exploiting sparsity.

Science.gov (United States)

Song, Chenchen; Martínez, Todd J

2016-05-07

We present a tensor hypercontracted (THC) scaled opposite spin second order Møller-Plesset perturbation theory (SOS-MP2) method. By using THC, we reduce the formal scaling of SOS-MP2 with respect to molecular size from quartic to cubic. We achieve further efficiency by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs) to accelerate integral construction and matrix multiplication. The practical scaling of GPU-accelerated atomic orbital-based THC-SOS-MP2 calculations is found to be N(2.6) for reference data sets of water clusters and alanine polypeptides containing up to 1600 basis functions. The errors in correlation energy with respect to density-fitting-SOS-MP2 are less than 0.5 kcal/mol for all systems tested (up to 162 atoms).

Nash equilibrium in differential games and the construction of the programmed iteration method

International Nuclear Information System (INIS)

Averboukh, Yurii V

2011-01-01

This work is devoted to the study of nonzero-sum differential games. The set of payoffs in a situation of Nash equilibrium is examined. It is shown that the set of payoffs in a situation of Nash equilibrium coincides with the set of values of consistent functions which are fixed points of the program absorption operator. A condition for functions to be consistent is given in terms of the weak invariance of the graph of the functions under a certain differential inclusion. Bibliography: 18 titles.

istSOS, a new sensor observation management system: software architecture and a real-case application for flood protection

Directory of Open Access Journals (Sweden)

M. Cannata

2015-11-01

Full Text Available istSOS (Istituto scienze della Terra Sensor Observation Service is an implementation of the Sensor Observation Service (SOS standard from the Open Geospatial Consortium. The development of istSOS started in 2009 in order to provide a simple implementation of the SOS for the management, provision and integration of hydro-meteorological data collected in Canton Ticino (Southern Switzerland. istSOS is an Open Source, entirely written in Python and based on reliable software like PostgreSQL/PostGIS and Apache/mod_wsgi. This paper illustrates the latest software enhancements, including a RESTful Web service and a Web-based graphical user interface, which enable a better and simplified interaction with measurements and SOS service settings. The robustness of the implemented solution has been validated in a real-case application: the Verbano Lake Early Warning System. In this application, near real-time data have to be exchanged by inter-regional partners and used in a hydrological model for lake level forecasting and flooding hazard assessment. This system is linked with a dedicated geoportal used by the civil protection for the management, alert and protection of the population and the assets of the Locarno area. Practical considerations, technical issues and foreseen improvements are presented and discussed.

Mutation-Specific Mechanisms of Hyperactivation of Noonan Syndrome SOS Molecules Detected with Single-molecule Imaging in Living Cells.

Science.gov (United States)

Nakamura, Yuki; Umeki, Nobuhisa; Abe, Mitsuhiro; Sako, Yasushi

2017-10-26

Noonan syndrome (NS) is a congenital hereditary disorder associated with developmental and cardiac defects. Some patients with NS carry mutations in SOS, a guanine nucleotide exchange factor (GEF) for the small GTPase RAS. NS mutations have been identified not only in the GEF domain, but also in various domains of SOS, suggesting that multiple mechanisms disrupt SOS function. In this study, we examined three NS mutations in different domains of SOS to clarify the abnormality in its translocation to the plasma membrane, where SOS activates RAS. The association and dissociation kinetics between SOS tagged with a fluorescent protein and the living cell surface were observed in single molecules. All three mutants showed increased affinity for the plasma membrane, inducing excessive RAS signalling. However, the mechanisms by which their affinity was increased were specific to each mutant. Conformational disorder in the resting state, increased probability of a conformational change on the plasma membrane, and an increased association rate constant with the membrane receptor are the suggested mechanisms. These different properties cause the specific phenotypes of the mutants, which should be rescuable with different therapeutic strategies. Therefore, single-molecule kinetic analyses of living cells are useful for the pathological analysis of genetic diseases.

Synthesis and initial biological evaluation of a novel Tc-99m radioligand as a potential agent for 5-HT1A receptor imaging

Energy Technology Data Exchange (ETDEWEB)

Abdelounis, Najoua Mejri; Saied, Nadia Malek; Essouissi, Imen; Guizani, Sihem; Saidi, Mouldi [CNSTN, Sidi Thabet (Tunisia). Research Unit of Medical, Agricultural and Environmental Use of Nuclear Applications

2014-09-01

The synthesis, characterization and biological evaluation of N-Tolueneferrocenecarboxamide labeled with technetium-99m ({sup 99m}Tc-TTCC) is reported. Biological studies in Wistar rats showed the ability of {sup 99m}Tc-TPCC to cross the intact blood-brain barrier. In vivo biodistribution indicated that this complex had good brain uptake (1.32%ID/g at 5 min and 0.64%ID/g at 60 min) and good retention (about 50% of the activity was retained in the brain at 60 min post-injection). Regional brain distribution study showed that hippocampus, where the 5-HT1A receptor density is high, had the highest uptake (0.73%ID/g at 5 min p.i.) and the cerebellum, where the 5-HT1A receptor density is low, had the lowest uptake (0.12%ID/gID/g at 5 min p.i.). After blocking with 8-hydroxy-2-(dipropylamino) tetralin, the uptake of hippocampus was decreased significantly from 0.73%ID/g to 0.20%ID/g at 5 min p.i., while the cerebellum had no significant decrease. This result indicates that 99mTc complex has specific binding to 5-HT1A receptor. (orig.)

Preparation and bioevaluation of 99Tcm-HYNIC-Annexin B1 as a novel radiotracer for apoptosis detection

International Nuclear Information System (INIS)

Luo Quanyong; Luo Qiong; Lu Hankui; Zhu Ruisen; Wang Fang; Zhang Yi; Sun Shuhan; Zhang Zhiyong; Liu Xingfeng

2008-01-01

Objective: Annexin B1, a novel Ca 2+ -dependent phosphatidylserine (PS)-binding protein, has been shown to have a high affinity for PS exposed on the surface of apoptotic cells or activated platelets. The aim of this study was to develop and bioevaluate an Annexin B1 based PS-targeting radiotracer labeled with 99 Tc m . Methods: Annexin B1 was indirectly labeled with 99 Tc m using hydrazinonicotinamide (HYNIC) as a bifunctional chelator agent. Binding assay with human activated platelets was used to evaluate the biological activity of 99 Tc m -HYNIC-Annexin B1 in vitro. The potential of 99 Tc m -HYNIC-Annexin B1 to detect apoptosis in vivo was evaluated in mice models with dexamethasone-inducecd thymus apoptosis and anti-Fas antibody induced liver apoptosis. The paired t-test was used to analyse the data. Results: The labeling procedure yielded a compound with radiochemical purity higher than 96% and good in vitro stability. Plate- lets binding assay indicated that 99 Tc m -HYNIC-Annexin B1 retained their PS binding activity in vitro. The percentage activity of injection dose per gram of tissue (% ID/g) of mouse thymus showed a 3.50-fold increase at 18 h after administration of dexamethasone compared with control mice (t=5.234, P 99 Tc m -HYNIC-Annexin B1 in the liver of anti-Fas antibody treated mice. The %ID/g of apoptotic murine liver showed a 2.02-fo1d increase at 2 h after the administration of anti-Fas antibody compared with control mice (t=6.178, P 99 Tc m -HYNIC-Annexin B1 can be prepared with high radiochemical purity and in vitro stability. These da- ta also suggest that 99 Tc m -HYNIC-Annexin B1 retains its in vitro and in vivo biological activities. It may therefore be useful as a novel radioligand for the noninvasive imaging of PS externalization associated with apoptosis. (authors)

A periodic point-based method for the analysis of Nash equilibria in 2 x 2 symmetric quantum games

International Nuclear Information System (INIS)

Schneider, David

2011-01-01

We present a novel method of looking at Nash equilibria in 2 x 2 quantum games. Our method is based on a mathematical connection between the problem of identifying Nash equilibria in game theory, and the topological problem of the periodic points in nonlinear maps. To adapt our method to the original protocol designed by Eisert et al (1999 Phys. Rev. Lett. 83 3077-80) to study quantum games, we are forced to extend the space of strategies from the initial proposal. We apply our method to the extended strategy space version of the quantum Prisoner's dilemma and find that a new set of Nash equilibria emerge in a natural way. Nash equilibria in this set are optimal as Eisert's solution of the quantum Prisoner's dilemma and include this solution as a limit case.

Over-expressing the soluble gp130-Fc does not ameliorate methionine and choline deficient diet-induced non alcoholic steatohepatitis in mice.

Directory of Open Access Journals (Sweden)

Helene L Kammoun

Full Text Available Non-alcoholic steatohepatitis (NASH is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6 has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet and hypothesized that markers of NASH would be ameliorated in such mice. Sgp130Fc Tg and littermate control mice were fed a MCD or control diet for 4 weeks. The MCD diet induced many hallmarks of NASH including hepatomegaly, steatosis, and liver inflammation. However, in contrast with other mouse models and, indeed, human NASH, the MCD diet model did not increase the mRNA or protein expression of IL-6. Not surprisingly, therefore, markers of MCD diet-induced NASH were unaffected by sgp130Fc transgenic expression. While the MCD diet model induces many pathophysiological markers of NASH, it does not induce increased IL-6 expression in the liver, a key hallmark of human NASH. We, therefore, caution the use of the MCD diet as a viable mouse model of NASH.

Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model

NARCIS (Netherlands)

Li, Jieyi; Chanda, Dipanjan; van Gorp, Patrick J.; Jeurissen, Mike L. J.; Houben, Tom; Walenbergh, Sofie M. A.; Debets, Jacques; Oligschlaeger, Yvonne; Gijbels, Marion J. J.; Neumann, Dietbert; Shiri-Sverdlov, Ronit

2016-01-01

Non-alcoholic steatohepatitis (NASH) is a common liver disease characterized by hepatic lipid accumulation (steatosis) and inflammation. Currently, therapeutic options are poor and the long-term burden to society is constantly increasing. Previously, macrophage stimulating protein (MSP)-a serum

Induction of the SOS response in ultraviolet-irradiated Escherichia coli analyzed by dynamics of LexA, RecA and SulA proteins

International Nuclear Information System (INIS)

Aksenov, S.V.

1999-01-01

The SOS response in Escherichia coli is induced after DNA-damaging treatments including ultraviolet light. Regulation of the SOS response is accomplished through specific interaction of the two SOS regulator proteins, LexA and RecA. In ultraviolet light treated cells nucleotide excision repair is the major system that removes the induced lesions from the DNA. Here, induction of the SOS response in Escherichia coli with normal and impaired excision repair function is studied by simulation of intracellular levels of regulatory LexA and RecA proteins, and SulA protein. SulA protein is responsible for SOS-inducible cell division inhibition. Results of the simulations show that nucleotide excision repair influences time-courses of LexA , RecA and SulA induction by modulating the dynamics of RecA protein distribution between its normal and SOS-activated forms

Kinetic and dose dependences of the SOS-induction in E.coli K-12 (uvrA) cells exposed to the different UV doses

International Nuclear Information System (INIS)

Komova, O.V.; Kandiano, E.S.; Malavya, G.

1999-01-01

The kinetic and dose dependences of the SOS-induction in E.coli (uvrA) cells exposed to UV light were investigated. Below 2 J/m 2 the rate of the SOS-induction increased with dose. The maximal level of the SOS-response was proportional to the UV dose. Pyrimidine dimers were necessary for the induction. In the dose range 2-10 J/m 2 the rate of the SOS-induction decreased with dose. The dose-response curve was non-linear. Pyrimidine dimers were not required for the induction. The nature of the molecular events leading to the SOS-induction at low and high UV doses was discussed. (author)

A Simple Diet- and Chemical-Induced Murine NASH Model with Rapid Progression of Steatohepatitis, Fibrosis and Liver Cancer.

Science.gov (United States)

Tsuchida, Takuma; Lee, Youngmin A; Fujiwara, Naoto; Ybanez, Maria; Allen, Brittany; Martins, Sebastiao; Fiel, M Isabel; Goossens, Nicolas; Chou, Hsin-I; Hoshida, Yujin; Friedman, Scott L

2018-03-20

Although the majority of patients with nonalcoholic fatty liver disease (NAFLD) have only steatosis without progression, a sizable fraction develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular carcinoma (HCC). Many established diet-induced mouse models for NASH require 24-52 weeks, which makes testing for drug response costly and time consuming. We have sought to establish a murine NASH model with rapid progression of extensive fibrosis and HCC by using a western diet (WD), which is high-fat, high-fructose and high-cholesterol, combined with low dose weekly intraperitoneal carbon tetrachloride (CCl 4 ), which served as an accelerator. C57BL/6J mice were fed a normal chow diet (ND) ± CCl 4 or WD ± CCl 4 for 12 and 24 weeks. Addition of CCl 4 exacerbated histological features of NASH, fibrosis, and tumor development induced by WD, which resulted in stage 3 fibrosis at 12 weeks and HCC development at 24 weeks. Furthermore, whole liver transcriptomic analysis indicated that dysregulated molecular pathways in WD/CCl 4 mice and immunologic features were closely similar to those of human NASH. Our mouse NASH model exhibits rapid progression of advanced fibrosis and HCC, and mimics histological, immunological and transcriptomic features of human NASH, suggesting that it will be a useful experimental tool for preclinical drug testing. A carefully characterized model has been developed in mice that recapitulates the progressive stages of human fatty liver disease, from simple steatosis, to inflammation, fibrosis and cancer. The functional pathways of gene expression and immune abnormalities in this model closely resemble human disease. The ease and reproducibility of this model makes it ideal to study disease pathogenesis and test new treatments. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Negotiating transfer pricing using the Nash bargaining solution

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Clempner Julio B.

2017-12-01

Full Text Available This paper analyzes and proposes a solution to the transfer pricing problem from the point of view of the Nash bargaining game theory approach. We consider a firm consisting of several divisions with sequential transfers, in which central management provides a transfer price decision that enables maximization of operating profits. Price transferring between divisions is negotiable throughout the bargaining approach. Initially, we consider a disagreement point (status quo between the divisions of the firm, which plays the role of a deterrent. We propose a framework and a method based on the Nash equilibrium approach for computing the disagreement point. Then, we introduce a bargaining solution, which is a single-valued function that selects an outcome from the feasible pay-offs for each bargaining problem that is a result of cooperation of the divisions of the firm involved in the transfer pricing problem. The agreement reached by the divisions in the game is the most preferred alternative within the set of feasible outcomes, which produces a profit-maximizing allocation of the transfer price between divisions. For computing the bargaining solution, we propose an optimization method. An example illustrating the usefulness of the method is presented.

No evidence of the genotoxic potential of gold, silver, zinc oxide and titanium dioxide nanoparticles in the SOS chromotest.

Science.gov (United States)

Nam, Sun-Hwa; Kim, Shin Woong; An, Youn-Joo

2013-10-01

Gold nanoparticles (Au NPs), silver nanoparticles (Ag NPs), zinc oxide nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO2 NPs) are widely used in cosmetic products such as preservatives, colorants and sunscreens. This study investigated the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using the SOS chromotest with Escherichia coli PQ37. The maximum exposure concentrations for each nanoparticle were 3.23 mg l(-1) for Au NPs, 32.3 mg l(-1) for Ag NPs and 100 mg l(-1) for ZnO NPs and TiO2 NPs. Additionally, in order to compare the genotoxicity of nanoparticles and corresponding dissolved ions, the ions were assessed in the same way as nanoparticles. The genotoxicity of the titanium ion was not assessed because of the extremely low solubility of TiO2 NPs. Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn, in a range of tested concentrations, exerted no effects in the SOS chromotest, evidenced by maximum IF (IFmax) values of below 1.5 for all chemicals. Owing to the results, nanosized Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn are classified as non-genotoxic on the basis of the SOS chromotest used in this study. To the best of our knowledge, this is the first study to evaluate the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using the SOS chromotest. Copyright © 2012 John Wiley & Sons, Ltd.

A periodic point-based method for the analysis of Nash equilibria in 2 x 2 symmetric quantum games

Energy Technology Data Exchange (ETDEWEB)

Schneider, David, E-mail: schneide@tandar.cnea.gov.ar [Departamento de Fisica, Comision Nacional de EnergIa Atomica. Av. del Libertador 8250, 1429 Buenos Aires (Argentina)

2011-03-04

We present a novel method of looking at Nash equilibria in 2 x 2 quantum games. Our method is based on a mathematical connection between the problem of identifying Nash equilibria in game theory, and the topological problem of the periodic points in nonlinear maps. To adapt our method to the original protocol designed by Eisert et al (1999 Phys. Rev. Lett. 83 3077-80) to study quantum games, we are forced to extend the space of strategies from the initial proposal. We apply our method to the extended strategy space version of the quantum Prisoner's dilemma and find that a new set of Nash equilibria emerge in a natural way. Nash equilibria in this set are optimal as Eisert's solution of the quantum Prisoner's dilemma and include this solution as a limit case.

The SOS-LUX-LAC-FLUORO-Toxicity-test on the International Space Station (ISS).

Science.gov (United States)

Rabbow, E; Rettberg, P; Baumstark-Khan, C; Horneck, G

2003-01-01

In the 21st century, an increasing number of astronauts will visit the International Space Station (ISS) for prolonged times. Therefore it is of utmost importance to provide necessary basic knowledge concerning risks to their health and their ability to work on the station and during extravehicular activities (EVA) in free space. It is the aim of one experiment of the German project TRIPLE-LUX (to be flown on the ISS) to provide an estimation of health risk resulting from exposure of the astronauts to the radiation in space inside the station as well as during extravehicular activities on one hand, and of exposure of astronauts to unavoidable or as yet unknown ISS-environmental genotoxic substances on the other. The project will (i) provide increased knowledge of the biological action of space radiation and enzymatic repair of DNA damage, (ii) uncover cellular mechanisms of synergistic interaction of microgravity and space radiation and (iii) examine the space craft milieu with highly specific biosensors. For these investigations, the bacterial biosensor SOS-LUX-LAC-FLUORO-Toxicity-test will be used, combining the SOS-LUX-Test invented at DLR Germany (Patent) with the commercially available LAC-FLUORO-Test. The SOS-LUX-Test comprises genetically modified bacteria transformed with the pBR322-derived plasmid pPLS-1. This plasmid carries the promoterless lux operon of Photobacterium leiognathi as a reporter element under control of the DNA-damage dependent SOS promoter of ColD as sensor element. This system reacts to radiation and other agents that induce DNA damages with a dose dependent measurable emission of bioluminescence of the transformed bacteria. The analogous LAC-FLUORO-Test has been developed for the detection of cellular responses to cytotoxins. It is based on the constitutive expression of green fluorescent protein (GFP) mediated by the bacterial protein expression vector pGFPuv (Clontech, Palo Alto, USA). In response to cytotoxic agents, this system

Leptospira interrogans serovar copenhageni harbors two lexA genes involved in SOS response.

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Luciane S Fonseca

Full Text Available Bacteria activate a regulatory network in response to the challenges imposed by DNA damage to genetic material, known as the SOS response. This system is regulated by the RecA recombinase and by the transcriptional repressor lexA. Leptospira interrogans is a pathogen capable of surviving in the environment for weeks, being exposed to a great variety of stress agents and yet retaining its ability to infect the host. This study aims to investigate the behavior of L. interrogans serovar Copenhageni after the stress induced by DNA damage. We show that L. interrogans serovar Copenhageni genome contains two genes encoding putative LexA proteins (lexA1 and lexA2 one of them being potentially acquired by lateral gene transfer. Both genes are induced after DNA damage, but the steady state levels of both LexA proteins drop, probably due to auto-proteolytic activity triggered in this condition. In addition, seven other genes were up-regulated following UV-C irradiation, recA, recN, dinP, and four genes encoding hypothetical proteins. This set of genes is potentially regulated by LexA1, as it showed binding to their promoter regions. All these regions contain degenerated sequences in relation to the previously described SOS box, TTTGN 5CAAA. On the other hand, LexA2 was able to bind to the palindrome TTGTAN10TACAA, found in its own promoter region, but not in the others. Therefore, the L. interrogans serovar Copenhageni SOS regulon may be even more complex, as a result of LexA1 and LexA2 binding to divergent motifs. New possibilities for DNA damage response in Leptospira are expected, with potential influence in other biological responses such as virulence.

99mTc-IgG-Lung Scintigraphy in the Assessment of Pulmonary Involvement in Interstitial Lung Disease and Its Comparison With Pulmonary Function Tests and High-Resolution Computed Tomography: A Preliminary Study

International Nuclear Information System (INIS)

Bahtouee, Mehrzad; Saberifard, Jamshid; Javadi, Hamid; Nabipour, Iraj; Malakizadeh, Hasan; Monavvarsadegh, Gholamhossein; Ilkhani Pak, Hoda; Sadeghi, Azadeh; Assadi, Majid

2015-01-01

The discrimination of inactive inflammatory processes from the active form of the disease is of great importance in the management of interstitial lung disease (ILD). The aim of this study was to determine the efficacy of 99mTc-IgG scan for the detection of severity of disease compared to high-resolution computed tomography (HRCT) and pulmonary function test (PFT). Eight known cases of ILD including four cases of Mustard gas (MG) intoxication and four patients with ILD of unknown cause were included in this study. A population of six patients without lung disease was considered as the control group. The patients underwent PFT and high-resolution computed tomography, followed by 99mTc-IgG scan. They were followed up for one year. 99mTc-IgG scan assessment of IgG uptake was accomplished both qualitatively (subjectively) and semiquantitatively. All eight ILD patients demonstrated a strong increase in 99mTc-IgG uptake in the lungs, compared to the control patients. The 99mTc-IgG scan scores were higher in the patient group (0.64[95% confidence interval(CI)=0.61-0.69])) than the control group (0.35 (0.35[95% CI=0.28-0.40]), (P<0.05)). In patients, a statistically significant positive correlation was detected between 99mTc-IgG scan and HRCT scores (Spearman’s correlation coefficient = 0.92, P < 0.008). The 99mTc-Human Immunoglobulin (HIG) scores were not significantly correlated with PFT findings (including FVC, FEV1, FEV1/FVC), O 2 saturation and age (P values > 0.05). There were no significant correlations between 99mTc-IgG score and HRCT patterns including ground glass opacity, reticular fibrosis and honeycombing (P value > 0.05). The present results confirmed that 99mTc-IgG scan could be applied to detect the severity of pulmonary involvement, which was well correlated with HRCT findings. This data also showed that the 99mTc-IgG scan might be used as a complement to HRCT in the functional evaluation of the clinical status in ILD; however, further studies are

Is the S.O.S. diagnostic algorithm applicable to creating highly safe protective systems?

International Nuclear Information System (INIS)

Drab, F.

1994-01-01

The S.O.S. diagnostic system is analyzed and compared with KOMPARACE and MIN-MAX type diagnostic systems. Designed for the identification of failed sensors, the S.O.S. dynamic algorithm is based on a digital monitoring of output signals from a pair of sensors measuring the same technological parameter. The last 3 output signal data from the two sensors are stored in the algorithm memory. The analysis indicates that S.O.S. is no major achievement in the field of diagnosis because its properties are nearly identical with those of the conventional MIN-MAX system. Some degradation failures of the sensor are incorrectly interpreted by the new algorithm, some failures are not detected at all. From this point of view the new algorithm is inferior to the KOMPARACE type algorithm. (J.B.). 2 figs., 5 refs

Development of instant kits 99Tcm-labelling of anti-CEA antibody and hIgG for scintigraphy

International Nuclear Information System (INIS)

Boonkittcharoen, V.

1998-01-01

99 Tc m -labelled monoclonal antibodies (MAbs) and human immunoglobulins (hIgG) have recently emerged as a new class of site specific radiopharmaceuticals. The role of 99 Tc m -labelled MAbs particularly anti-CEA IgG in tumour imaging has essentially established for early revealing of occult lesions in patients. Superiority of the method over X ray CT has been addressed for its capability in differentiating post-operation fibrosis from viable tumour. At present data, instant kits for preparation of this particular class of radiopharmaceuticals can be obtained from commercial sources but unfortunately at high prices. This prohibits the use of these promising diagnostic agents in developing country like Thailand. Under the assistance from IAEA through a research coordinating program, we worked on the 99 Tc m -radiochemistry in immunoglobulin labelling to establish the knowledge and acquire the know how in the development of in-house instant kits at low cost to serve the local nuclear medicine clinics in diagnosis of infectious and neoplastic diseases

Identification of genes involved in low aminoglycoside-induced SOS response in Vibrio cholerae: a role for transcription stalling and Mfd helicase.

Science.gov (United States)

Baharoglu, Zeynep; Babosan, Anamaria; Mazel, Didier

2014-02-01

Sub-inhibitory concentrations (sub-MIC) of antibiotics play a very important role in selection and development of resistances. Unlike Escherichia coli, Vibrio cholerae induces its SOS response in presence of sub-MIC aminoglycosides. A role for oxidized guanine residues was observed, but the mechanisms of this induction remained unclear. To select for V. cholerae mutants that do not induce low aminoglycoside-mediated SOS induction, we developed a genetic screen that renders induction of SOS lethal. We identified genes involved in this pathway using two strategies, inactivation by transposition and gene overexpression. Interestingly, we obtained mutants inactivated for the expression of proteins known to destabilize the RNA polymerase complex. Reconstruction of the corresponding mutants confirmed their specific involvement in induction of SOS by low aminoglycoside concentrations. We propose that DNA lesions formed on aminoglycoside treatment are repaired through the formation of single-stranded DNA intermediates, inducing SOS. Inactivation of functions that dislodge RNA polymerase leads to prolonged stalling on these lesions, which hampers SOS induction and repair and reduces viability under antibiotic stress. The importance of these mechanisms is illustrated by a reduction of aminoglycoside sub-MIC. Our results point to a central role for transcription blocking at DNA lesions in SOS induction, so far underestimated.

Apoptosis-like death, an extreme SOS response in Escherichia coli.

Science.gov (United States)

Erental, Ariel; Kalderon, Ziva; Saada, Ann; Smith, Yoav; Engelberg-Kulka, Hanna

2014-07-15

In bacteria, SOS is a global response to DNA damage, mediated by the recA-lexA genes, resulting in cell cycle arrest, DNA repair, and mutagenesis. Previously, we reported that Escherichia coli responds to DNA damage via another recA-lexA-mediated pathway resulting in programmed cell death (PCD). We called it apoptosis-like death (ALD) because it is characterized by membrane depolarization and DNA fragmentation, which are hallmarks of eukaryotic mitochondrial apoptosis. Here, we show that ALD is an extreme SOS response that occurs only under conditions of severe DNA damage. Furthermore, we found that ALD is characterized by additional hallmarks of eukaryotic mitochondrial apoptosis, including (i) rRNA degradation by the endoribonuclease YbeY, (ii) upregulation of a unique set of genes that we called extensive-damage-induced (Edin) genes, (iii) a decrease in the activities of complexes I and II of the electron transport chain, and (iv) the formation of high levels of OH˙ through the Fenton reaction, eventually resulting in cell death. Our genetic and molecular studies on ALD provide additional insight for the evolution of mitochondria and the apoptotic pathway in eukaryotes. Importance: The SOS response is the first described and the most studied bacterial response to DNA damage. It is mediated by a set of two genes, recA-lexA, and it results in DNA repair and thereby in the survival of the bacterial culture. We have shown that Escherichia coli responds to DNA damage by an additional recA-lexA-mediated pathway resulting in an apoptosis-like death (ALD). Apoptosis is a mode of cell death that has previously been reported only in eukaryotes. We found that E. coli ALD is characterized by several hallmarks of eukaryotic mitochondrial apoptosis. Altogether, our results revealed that recA-lexA is a DNA damage response coordinator that permits two opposite responses: life, mediated by the SOS, and death, mediated by the ALD. The choice seems to be a function of the degree

Canagliflozin, an SGLT2 inhibitor, attenuates the development of hepatocellular carcinoma in a mouse model of human NASH.

Science.gov (United States)

Shiba, Kumiko; Tsuchiya, Kyoichiro; Komiya, Chikara; Miyachi, Yasutaka; Mori, Kentaro; Shimazu, Noriko; Yamaguchi, Shinobu; Ogasawara, Naomi; Katoh, Makoto; Itoh, Michiko; Suganami, Takayoshi; Ogawa, Yoshihiro

2018-02-05

Sodium glucose cotransporter 2 (SGLT2) inhibitors, an antidiabetic drug, promotes urinary excretion of glucose by blocking its reabsorption in the renal proximal tubules. It is unclear whether SGLT2 inhibition could attenuate nonalcoholic steatohepatitis (NASH) and NASH-associated hepatocellular carcinoma. We examined the preventive effects of an SGLT2 inhibitor canagliflozin (CANA) in Western diet (WD)-fed melanocortin 4 receptor-deficient (MC4R-KO) mice, a mouse model of human NASH. An eight-week CANA treatment attenuated hepatic steatosis in WD-fed MC4R-KO mice, with increased epididymal fat mass without inflammatory changes. CANA treatment for 20 weeks inhibited the development of hepatic fibrosis in WD-fed MC4R-KO mice. After one year of CANA treatment, the number of liver tumors was significantly reduced in WD-fed MC4R-KO mice. In adipose tissue, CANA suppressed the ratio of oxidative to reduced forms of glutathiones (GSSG/GSH) in WD-fed MC4R-KO mice. Treatment with GSH significantly attenuated the H 2 O 2 -induced upregulation of genes related to NADPH oxidase in 3T3-L1 adipocytes, and that of Il6, Tgfb, and Pdgfb in RAW264.7 cells. This study provides evidence that SGLT2 inhibitors represent the unique class of drugs that can attenuate or delay the onset of NASH and eventually hepatocellular carcinoma, at least partly, through "healthy adipose expansion".

Critical Realism and Statistical Methods--A Response to Nash

Science.gov (United States)

Scott, David

2007-01-01

This article offers a defence of critical realism in the face of objections Nash (2005) makes to it in a recent edition of this journal. It is argued that critical and scientific realisms are closely related and that both are opposed to statistical positivism. However, the suggestion is made that scientific realism retains (from statistical…

Radiolabelling of glycosylated MFE-23::CPG2 fusion protein (MFECP1) with 99mTc for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT).

Science.gov (United States)

Francis, R J; Mather, S J; Chester, K; Sharma, S K; Bhatia, J; Pedley, R B; Waibel, R; Green, A J; Begent, R H J

2004-08-01

MFECP1 is a glycosylated recombinant fusion protein composed of MFE-23, a high-affinity anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), fused to the enzyme carboxypeptidase G2 (CPG2), and has been constructed for use in antibody-directed enzyme pro-drug therapy (ADEPT). Radiolabelling of glycosylated MFECP1 with technetium-99m was developed for the purpose of determining tumour localisation of MFECP1 in a phase I ADEPT clinical study. The method used was 99mTc-carbonyl [99mTc(H2O)3(CO)3]+ (abbreviated to TcCO) mediated labelling of 99mTc to the hexahistidine (His) tag of MFECP1. MFECP1 fusion protein was labelled with TcCO under a variety of conditions, and this was shown to be a relatively simple and robust method. Tissue biodistribution was assessed in a CEA-expressing LS174T (human colon carcinoma) nude mouse xenograft model. Tissues were taken at 1, 4 and 6 h for assessment of distribution of radioactivity and for measurement of CPG2 enzyme levels. The amount of radioactivity retained by the tumour proved to be an accurate estimation of actual measured enzyme activity, indicating that this radiolabelling method does not appear to damage the antibody-antigen binding or the enzyme activity of MFECP1. However, correlation between CPG2 enzyme activity and measured radioactivity in liver, spleen and kidney was poor, indicating retention of radioactivity in non-tumour sites but loss of enzyme activity. The high retention of technetium radioisotope in normal tissues may limit the clinical applicability of this radiolabelling method for MFECP1; however, these results suggest that this technique does have applicability for measuring the biodistribution of His-tagged recombinant proteins.

Radiolabelling of glycosylated MFE-23::CPG2 fusion protein (MFECP1) with 99mTc for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT)

International Nuclear Information System (INIS)

Francis, R.J.; Chester, K.; Sharma, S.K.; Bhatia, J.; Pedley, R.B.; Green, A.J.; Begent, R.H.J.; Mather, S.J.; Waibel, R.

2004-01-01

MFECP1 is a glycosylated recombinant fusion protein composed of MFE-23, a high-affinity anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), fused to the enzyme carboxypeptidase G2 (CPG2), and has been constructed for use in antibody-directed enzyme pro-drug therapy (ADEPT). Radiolabelling of glycosylated MFECP1 with technetium-99m was developed for the purpose of determining tumour localisation of MFECP1 in a phase I ADEPT clinical study. The method used was 99m Tc-carbonyl [ 99m Tc(H 2 O) 3 (CO) 3 ] + (abbreviated to TcCO) mediated labelling of 99m Tc to the hexahistidine (His) tag of MFECP1. MFECP1 fusion protein was labelled with TcCO under a variety of conditions, and this was shown to be a relatively simple and robust method. Tissue biodistribution was assessed in a CEA-expressing LS174T (human colon carcinoma) nude mouse xenograft model. Tissues were taken at 1, 4 and 6 h for assessment of distribution of radioactivity and for measurement of CPG2 enzyme levels. The amount of radioactivity retained by the tumour proved to be an accurate estimation of actual measured enzyme activity, indicating that this radiolabelling method does not appear to damage the antibody-antigen binding or the enzyme activity of MFECP1. However, correlation between CPG2 enzyme activity and measured radioactivity in liver, spleen and kidney was poor, indicating retention of radioactivity in non-tumour sites but loss of enzyme activity. The high retention of technetium radioisotope in normal tissues may limit the clinical applicability of this radiolabelling method for MFECP1; however, these results suggest that this technique does have applicability for measuring the biodistribution of His-tagged recombinant proteins. (orig.)

The SOS response is permitted in Escherichia coli strains deficient in the expression of the mazEF pathway.

Science.gov (United States)

Kalderon, Ziva; Kumar, Sathish; Engelberg-Kulka, Hanna

2014-01-01

The Escherichia coli (E. coli) SOS response is the largest, most complex, and best characterized bacterial network induced by DNA damage. It is controlled by a complex network involving the RecA and LexA proteins. We have previously shown that the SOS response to DNA damage is inhibited by various elements involved in the expression of the E. coli toxin-antitoxin mazEF pathway. Since the mazEF module is present on the chromosomes of most E. coli strains, here we asked: Why is the SOS response found in so many E. coli strains? Is the mazEF module present but inactive in those strains? We examined three E. coli strains used for studies of the SOS response, strains AB1932, BW25113, and MG1655. We found that each of these strains is either missing or inhibiting one of several elements involved in the expression of the mazEF-mediated death pathway. Thus, the SOS response only takes place in E. coli cells in which one or more elements of the E. coli toxin-antitoxin module mazEF or its downstream pathway is not functioning.

Dosimetric evaluation of 99mTc IgG as infection diagnostic agent for HIV positive patients

International Nuclear Information System (INIS)

Teran, Mariella; Paolino, Andrea; Vilar, Javier; Kapitan, Miguel; Andruskevicius, Patricia; Hermida, Juan C.; Gaudiano, Javier; Perez Sartori, Graciela; Savio Larriera, Eduardo

2008-01-01

A wide variety of radiopharmaceuticals are used as diagnostic or therapeutic agents. In this case 99m Tc-IgG was used to determine infection-inflammation processes in HIV patients, who sometimes are difficult to diagnose because of the presence of non specific signs and symptoms. The aim of this work was to estimate the hazard associated with the use of radiopharmaceuticals in nuclear medicine. In order to establish a proper design of kinetic studies and determine the radiation doses to individual human organs internal dosimetry methods were used. HIV positive patients with suspect of infection focus were administered via iv injection with 740 MBq (20 mCi) of 99m Tc-IgG. Anterior and posterior whole body images were acquired at 4 and 24 hours post injection in a gamma camera Mediso Medical Imaging, 1024 x 512 matrix. Geometric mean was calculated for different regions of interest taking into account decay, scattering and attenuation corrections. Blood and urine samples were collected at 1, 4, 8, 12 and 24 hours post injection. They were measured in a dose calibrator Capintec CR 5, corrections for geometry and decay were performed. For each patient, percentage of injected dose was calculated both for biological and image samples. The number of disintegrations was developed for those organs where higher concentration of activity was observed (liver, kidneys and spleen), the organs involved in the excretion (urinary bladder and intestines), red marrow and the reminder of the body. Total doses were estimated using OLINDA/EXM software. The code calculations showed that chosen organs as more compromised during the diagnostic procedure received very low effective doses. Correlation studies with calculations performed both for image and biological samples data were done. Despite the risk population under study the dosimetric estimations showed that 99m Tc-IgG is a safe radiopharmaceutical to be used in routine diagnostic procedures without hazardous effects. (author)

Implications of Nash Bargaining for Horizontal Industry Integration

OpenAIRE

Richard E. Just; Siddhartha Mitra; Sinaia Netanyahu

2005-01-01

This article shows how horizontal industry integration can arise from transferable asymmetry of technologies and endowments. The Nash bargaining solution suggests that greater technological diversity among coordinating parties yields greater gains from horizontal integration. The framework fits the case where a firm with a superior technology franchises the technology by horizontal integration. The results appear to fit hog production where integration has been primarily horizontal and, in pa...

Investigation of potential genotoxic activity using the SOS Chromotest for real paracetamol wastewater and the wastewater treated by the Fenton process.

Science.gov (United States)

Kocak, Emel

2015-01-01

The potential genotoxic activity associated with high strength real paracetamol (PCT) wastewater (COD = 40,000 mg/L, TOC = 12,000 mg/L, BOD5 = 19,320 mg/L) from a large-scale drug-producing plant in the Marmara Region, was investigated in pre- and post- treated wastewater by the Fenton process (COD = 2,920 mg/L, TOC = 880 mg/L; BOD5 = 870 mg/L). The SOS Chromotest, which is based on Escherichia coli PQ37 activities, was used for the assessment of genotoxicity. The corrected induction factors (CIF) values used as quantitative measurements of the genotoxic activity were obtained from a total of four different dilutions (100, 50, 6.25, and 0.078 % v/v.) for two samples, in triplicate, to detect potentially genotoxic activities with the SOS Chromotest. The results of the SOS Chromotest demonstrated CIFmax value of 1.24, indicating that the PCT effluent (non-treated) is genotoxic. The results of the SOS Chromotest showed an CIFmax value of 1.72, indicating that the wastewater treated by Fenton process is genotoxic. The findings of this study clearly reveal that the PCT wastewater (non-treated) samples have a potentially hazardous impact on the aquatic environment before treatment, and in the wastewater that was treated by the Fenton process, genotoxicity generally increased.

Scintigraphy with 99mTc labelled polyclonal human IgG in rheumatoid arthritis patients

International Nuclear Information System (INIS)

Stanchev, V.; Batalov, A.; Atanasov, A.

1999-01-01

The study design to assess the diagnostic relevance of scintigraphy with 99m Tc labelled polyclonal human IgG (HIG) for detecting active synovitis in rheumatoid arthritis patients. Fifteen patients presenting rheumatoid arthritis and 3 healthy volunteers are studied on digital camera (Diacam, Siemens). Following iv injection of 500 MBq 99m Tc - HIG, a 3- phase scintigraphy of the knee joints is performed and 4 hours later multiple planar views of the peripheral joint are recorded. Scintigraphic data are comparatively studied with the clinical indicators pointing to active synovitis - joint swellings and pain. Markedly expressed 99m Tc - HIG uptake is noted in joints apparently the most actively involved in the arthritis process clinically, whereas most of the joints without evidence of active synovitis revealed background activity only. The obtained scintigraphic results correlate strongly with the clinical indicator joint swelling (93.2%), and somewhat less with the presence of pain (81.5%). 13.5 per cent of the joints without clinically detectable swelling and 25.6% those free of pain are HIG-positive. 99m Tc - HIG scintigraphy is a highly sensitive noninvasive method of detecting active synovitis, promoting objective assessment of the joint inflammatory process in the course of treatment and follow-up study of rheumatoid arthritis patients

A Numerical Algorithm to find All Scalar Feedback Nash Equilibria

NARCIS (Netherlands)

Engwerda, J.C.

2013-01-01

Abstract: In this note we generalize a numerical algorithm presented in [9] to calculate all solutions of the scalar algebraic Riccati equations that play an important role in finding feedback Nash equilibria of the scalar N-player linear affine-quadratic differential game. The algorithm is based on

Analysis of SOS-Induced Spontaneous Prophage Induction in Corynebacterium glutamicum at the Single-Cell Level

Science.gov (United States)

Nanda, Arun M.; Heyer, Antonia; Krämer, Christina; Grünberger, Alexander; Kohlheyer, Dietrich

2014-01-01

The genome of the Gram-positive soil bacterium Corynebacterium glutamicum ATCC 13032 contains three integrated prophage elements (CGP1 to -3). Recently, it was shown that the large lysogenic prophage CGP3 (∼187 kbp) is excised spontaneously in a small number of cells. In this study, we provide evidence that a spontaneously induced SOS response is partly responsible for the observed spontaneous CGP3 induction. Whereas previous studies focused mainly on the induction of prophages at the population level, we analyzed the spontaneous CGP3 induction at the single-cell level using promoters of phage genes (Pint2 and Plysin) fused to reporter genes encoding fluorescent proteins. Flow-cytometric analysis revealed a spontaneous CGP3 activity in about 0.01 to 0.08% of the cells grown in standard minimal medium, which displayed a significantly reduced viability. A PrecA-eyfp promoter fusion revealed that a small fraction of C. glutamicum cells (∼0.2%) exhibited a spontaneous induction of the SOS response. Correlation of PrecA to the activity of downstream SOS genes (PdivS and PrecN) confirmed a bona fide induction of this stress response rather than stochastic gene expression. Interestingly, the reporter output of PrecA and CGP3 promoter fusions displayed a positive correlation at the single-cell level (ρ = 0.44 to 0.77). Furthermore, analysis of the PrecA-eyfp/Pint2-e2-crimson strain during growth revealed the highest percentage of spontaneous PrecA and Pint2 activity in the early exponential phase, when fast replication occurs. Based on these studies, we postulate that spontaneously occurring DNA damage induces the SOS response, which in turn triggers the induction of lysogenic prophages. PMID:24163339

RASISME DALAM FILM 99 CAHAYA DI LANGIT EROPA PART 1 (ANALISIS SEMIOTIKA DALAM FILM 99 CAHAYA DI LANGIT EROPA PART 1

Directory of Open Access Journals (Sweden)

Vallen Nur Rita

2016-09-01

Full Text Available Stereotip merupakan pernyataan negatif dari prasangka. Prasangka inilah yang kemudian dijadikan alasan untuk melakukan diskriminasi terhadap kelompok rasial tertentu. Stereotip dan prasangka kemudian merujuk pada suatu paham yang mempercayai adanya superioritas yang menolak adanya kesetaraan manusia yaitu rasisme. Perilaku maupun tindakan rasisme tersebut banyak muncul dalam beberapa scene film 99 Cahaya Di Langit Eropa Part 1. Tujuan dari penelitian ini adalah untuk mengetahui bagaimana simbol-simbol digunakan untuk menggambarkan rasisme di dalam film 99 Cahaya Di Langit Eropa Part 1. Metode yang digunakan oleh peneliti adalah semiotika Roland Barthes. Model Roland Barthes terdiri dari tiga tahap analisis yaitu denotasi, konotasi, mitos. Peneliti melakukan analisis menggunakan tanda verbal dan nonverbal yang terdapat dalam film “99 Cahaya di Langit Eropa Part 1”. Dalam menganalisis film 99 Cahaya di Langit Eropa Part 1, dikelompokkan menjadi beberapa kategori yang berhubungan dengan perilaku rasisme, antara lain : stereotip, prasangka, diskriminasi

37 CFR 1.99 - Third-party submission in published application.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Third-party submission in published application. 1.99 Section 1.99 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND... Provisions Information Disclosure Statement § 1.99 Third-party submission in published application. (a) A...

Influence of very short patch mismatch repair on SOS inducing lesions after aminoglycoside treatment in Escherichia coli.

Science.gov (United States)

Baharoglu, Zeynep; Mazel, Didier

2014-01-01

Low concentrations of aminoglycosides induce the SOS response in Vibrio cholerae but not in Escherichia coli. In order to determine whether a specific factor present in E. coli prevents this induction, we developed a genetic screen where only SOS inducing mutants are viable. We identified the vsr gene coding for the Vsr protein of the very short patch mismatch repair (VSPR) pathway. The effect of mismatch repair (MMR) mutants was also studied. We propose that lesions formed upon aminoglycoside treatment are preferentially repaired by VSPR without SOS induction in E. coli and by MMR when VSPR is impaired. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

The development of 99mTc-d, 1-HM-PAO

International Nuclear Information System (INIS)

Bai Lanqin; Huang Jinjie; Fan Li; Bai Suzhen; Li Guoli; Jing Hui; Xiao Lun

1991-12-01

The 99m Tc-d,1-HM-PAO is an ideal radiopharmaceutical for regional cerebral blood perfusion imaging. The improvement of synthesis and separation of diastereoisomers leads to obtain high purity (>99%) of d, 1-HM-PAO and meso-HM-PAO. During separation H NMR spectroscopy was used to monitor the relative composition of these two diastereoisomers that can ensure the purity of pligand of d,1-HM-PAO. The intravenous injection of 99m Tc-d,1-HM-PAO was formed by adding fresh 99m Tc washing liquor into a sterile. Pyrogen-free and freeze-dried vial. The radiochemical purity (RCP) of 99m Tc-d,1-HM-PAO was greater than 80%. From the experiments of 99m Tc-d,1-HM-PAO in mice, after two minutes of intravenously (I>V>) administration about 2.24% of injected dose (I.D.)appeared in the brain, and after 24 hours about 72% of radioactivity of injected dose still left in the brain. But for the 99m Tc-meso-HM-PAO after two minutes of i.v. administration, about 1.93% of I.D. appeared in the brain, and 24 hours later, 25% of radioactivity of I.D. was in the brain. This result shows that in the brain the radioactivity of 99m Tc-meso-HM-PAO declines faster than that of 99m Td-d,1-HM-PAO

Nash, el último fundador de la teoría de juegos, y la evolución del concepto de equilibrio desde Cournot

OpenAIRE

Streb, Jorge M.

2015-01-01

Nash recibió el premio Nobel de economía por dos aportes fundamentales: la distinción entre juegos cooperativos y no cooperativos, y el concepto de solución básico para juegos no cooperativos. Myerson indica que este equilibrio es el concepto de solución básico de teoría de juegos dado que, como señala Nash, los juegos cooperativos se pueden reducir a un juego no cooperativo más amplio agregando la negociación previa. El equilibrio de Nash puede verse también como equilibrio de Cournot-Nash p...

Generator of 99m Tc with MnO2 as support of 99 Mo

International Nuclear Information System (INIS)

Granados C, F.; Serrano G, J.

2002-01-01

The generator of 99m Tc with MnO 2 as support of 99 Mo was studied. By mean of static experiments the retention of 99 Mo in MnO 2 in function of the stirring time and of the p H value of the solution of 99 Mo. It was found that the 99 Mo presents 100% of retention in MnO 2 in the rank of p H 3-11 and the balance was reached before of 10 minutes. In dynamic conditions the retention of 99 Mo in MnO 2 at p H=5 was also higher: 99.72%. The generated 99m Tc can be separated from 99 Mo, adsorbed in MnO 2 packed in the column, using distilled water at p H=5 or NaCl solution at 0.9%. With saline solution the elution yields were greater than 80% and only an aliquot of 5 ml was necessary for obtaining this yield. The better results were obtained when the column was packed with 1 g of MnO 2 . The water and the saline solution were passed through of the column with a flux of 1.25 ml/min. (Author)

Nonalcoholic steatohepatitic (NASH) mice are protected from higher hepatotoxicity of acetaminophen upon induction of PPARα with clofibrate

International Nuclear Information System (INIS)

Donthamsetty, Shashikiran; Bhave, Vishakha S.; Mitra, Mayurranjan S.; Latendresse, John R.; Mehendale, Harihara M.

2008-01-01

The objective was to investigate if the hepatotoxic sensitivity in nonalcoholic steatohepatitic mice to acetaminophen (APAP) is due to downregulation of nuclear receptor PPARα via lower cell division and tissue repair. Male Swiss Webster mice fed methionine and choline deficient diet for 31 days exhibited NASH. On the 32nd day, a marginally toxic dose of APAP (360 mg/kg, ip) yielded 70% mortality in steatohepatitic mice, while all non steatohepatitic mice receiving the same dose survived. 14 C-APAP covalent binding, CYP2E1 protein, and enzyme activity did not differ from the controls, obviating increased APAP bioactivation as the cause of amplified APAP hepatotoxicity. Liver injury progressed only in steatohepatitic livers between 6 and 24 h. Cell division and tissue repair assessed by 3 H-thymidine incorporation and PCNA were inhibited only in the steatohepatitic mice given APAP suggesting that higher sensitivity of NASH liver to APAP-induced hepatotoxicity was due to lower tissue repair. The hypothesis that impeded liver tissue repair in steatohepatitic mice was due to downregulation of PPARα was tested. PPARα was downregulated in NASH. To investigate whether downregulation of PPARα in NASH is the critical mechanism of compromised liver tissue repair, PPARα was induced in steatohepatitic mice with clofibrate (250 mg/kg for 3 days, ip) before injecting APAP. All clofibrate pretreated steatohepatitic mice receiving APAP exhibited lower liver injury, which did not progress and the mice survived. The protection was not due to lower bioactivation of APAP but due to higher liver tissue repair. These findings suggest that inadequate PPARα expression in steatohepatitic mice sensitizes them to APAP hepatotoxicity

Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS.

Science.gov (United States)

Huang, William Y C; Yan, Qingrong; Lin, Wan-Chen; Chung, Jean K; Hansen, Scott D; Christensen, Sune M; Tu, Hsiung-Lin; Kuriyan, John; Groves, Jay T

2016-07-19

The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor-bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes. Single-molecule dwell time distributions reveal two, well-differentiated kinetic species for both Grb2 and SOS on the LAT assemblies. The majority fraction of membrane-recruited Grb2 and SOS both exhibit fast kinetics and single exponential dwell time distributions, with average dwell times of hundreds of milliseconds. The minor fraction exhibits much slower kinetics, extending the dwell times to tens of seconds. Considering this result in the context of the multistep process by which the Ras GEF (guanine nucleotide exchange factor) activity of SOS is activated indicates that kinetic stabilization from the LAT assembly may be important. This kinetic proofreading effect would additionally serve as a stochastic noise filter by reducing the relative probability of spontaneous SOS activation in the absence of receptor triggering. The generality of receptor-mediated assembly suggests that such effects may play a role in multiple receptor proximal signaling processes.

Architecture and performance of radiation-hardened 64-bit SOS/MNOS memory

International Nuclear Information System (INIS)

Kliment, D.C.; Ronen, R.S.; Nielsen, R.L.; Seymour, R.N.; Splinter, M.R.

1976-01-01

This paper discusses the circuit architecture and performance of a nonvolatile 64-bit MNOS memory fabricated on silicon on sapphire (SOS). The circuit is a test vehicle designed to demonstrate the feasibility of a high-performance, high-density, radiation-hardened MNOS/SOS memory. The array is organized as 16 words by 4 bits and is fully decoded. It utilizes a two-(MNOS) transistor-per-bit cell and differential sensing scheme and is realized in PMOS static resistor load logic. The circuit was fabricated and tested as both a fast write random access memory (RAM) and an electrically alterable read only memory (EAROM) to demonstrate design and process flexibility. Discrete device parameters such as retention, circuit electrical characteristics, and tolerance to total dose and transient radiation are presented

Expresión génica en pacientes obesos con enfermedad hepática por depósito de grasa Gene expression in obese patients with non-alcoholic steatohepatitis

Directory of Open Access Journals (Sweden)

A. Cayón

2008-04-01

Full Text Available La fisiopatología de la enfermedad hepática por depósito de grasa sólo se conoce de forma parcial. En este trabajo hemos analizado la expresión génica intrahepática de citoquinas, quimioquinas, receptores celulares, factores de crecimiento, transductores de señales intracelulares y proteínas de comunicación extracelular en el tejido hepático de sujetos obesos con y sin esteatohepatitis no alcohólica, en un intento de determinar un perfil de expresión génica asociado a las formas severas de la esteatohepatitis no alcohólica (EHNA. Se analizó un grupo de 38 pacientes obesos con un IMC > 35, que fueron sometidos a cirugía bariátrica. La expresión génica intrahepática se determinó en el tejido hepático dividiendo a los pacientes en tres grupos: a pacientes obesos sin datos histológicos sugestivos de EHNA (n = 12; b pacientes con EHNA sin fibrosis (n = 13; y c pacientes con EHNA y fibrosis (n = 13. Se consideró que existía una sobreexpresión génica cuando la diferencia en la expresión era, al menos, de dos veces con respecto al grupo control. Los resultados se confirmaron mediante PCR en tiempo real. Se detectó una expresión diferencial de 14 genes (10 sobreexpresados y 4 infraexpresados. Los genes sobreexpresados incluyeron prohibitina, TNF, TNF RI (p55, MCSF, R2-TRAIL, TGF-b1, CTGF, FGF, VEGF, BIGH3 y ObRb. La expresión de los genes insulin growth factor-1, insulin growth factor-2, interleuquina-2 y tyrosine-receptor fue menor que en el grupo control. En conclusión: 1. Los pacientes obesos con EHNA sin fibrosis muestran una sobreexpresión de genes proinflamatorios y proapoptóticos. En los pacientes con EHNA y fibrosis, se observa, además, una sobreexpresión de genes profibrogénicos, incluyendo el gen del receptor de la leptina. 2. La expresión de prohibitiva en los pacientes con EHNA, tanto con fibrosis como sin fibrosis, fue superior que en los controles, lo que sugiere una disfunción mitocondrial en los

Single d(ApG)/cis-diamminedichloroplatinum(II) adduct-induced mutagenesis in Escherichia coli

International Nuclear Information System (INIS)

Burnouf, D.; Fuchs, R.P.P.; Gauthier, C.; Chottard, J.C.

1990-01-01

The mutation spectrum induced by the widely used antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) showed that cisDDP[d(ApG)] adducts, although they account for only 25% of the lesions formed are ∼5 times more mutagenic than the major GG adduct. The authors report the construction of vectors bearing a single cisDDP[d(ApG)] lesion and their use in mutagenesis experiments in Escherichia coli. The mutagenic processing of the lesion is found to depend strictly on induction of the SOS system of the bacterial host cells. In SOS-induced cells, mutation frequencies of 1-2% were detected. All these mutations are targeted to the 5' base of the adduct. Single A → T transversions are mainly observed (80%), whereas A → G transitions account for 10% of the total mutations. Tandem base-pair substitutions involving the adenine residue and the thymine residue immediately 5' to the adduct occur at a comparable frequency (10%). No selective loss of the strand bearing the platinum adduct was seen, suggesting that, in vivo, cisDDP[d(ApG)] adducts are not blocking lesions. The high mutation specificity of cisDDP-[d(ApG)]-induced mutagenesis is discussed in relation to structural data

Information Structures in Nash and Leader-Follower Strategies.

Science.gov (United States)

1981-01-01

OICkASSIPICATION/ OOWNGRAOING IS. OISTNIIIUTION STATEMINT (ao tD. esPort ) * Approved for public release; distribution unlimited. 17. DISTRIBUTION STATEMENT...problems and two market models of duopoly ith this type of information structure are extensively analyzed and examined. DO jAN7, 1473 EDIION OF NV SS IS...information 3 structure is employed in both Nash games and optimal coordination problems and two market models of duopoly with this type of information

PPARα activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH.

Science.gov (United States)

Baron, Morgane; Leroyer, Aurélie S; Majd, Zouher; Lalloyer, Fanny; Vallez, Emmanuelle; Bantubungi, Kadiombo; Chinetti-Gbaguidi, Giulia; Delerive, Philippe; Boulanger, Chantal M; Staels, Bart; Tailleux, Anne

2011-09-01

Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are complex pathologies characterized by lipid accumulation, chronic inflammation and extensive tissue remodelling. Microparticles (MPs), small membrane vesicles produced by activated and apoptotic cells, might not only be biomarkers, but also functional actors in these pathologies. The apoE2-KI mouse is a model of atherosclerosis and NAFLD. Activation of the nuclear receptor PPARα decreases atherosclerosis and components of non-alcoholic steatohepatitis (NASH) in the apoE2-KI mouse. (1) To determine whether MPs are present in atherosclerotic lesions, liver and plasma during atherosclerosis and NASH progression in apoE2-KI mice, and (2) to study whether PPARα activation modulates MP concentrations. ApoE2-KI mice were fed a Western diet to induce atherosclerosis and NASH. MPs were isolated from atherosclerotic lesions, liver and blood and quantified by flow cytometry. An increase of MPs was observed in the atherosclerotic lesions and in the liver of apoE2-KI mice upon Western diet feeding. PPARα activation with fenofibrate decreased MP levels in the atherosclerotic lesions in a PPARα-dependent manner, but did not influence MP concentrations in the liver. Here we report that MPs are present in atherosclerotic lesions and in the liver of apoE2-KI mice. Their concentration increased during atherosclerosis and NASH development. PPARα activation differentially modulates MP levels in a tissue-specific manner. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Existence and Policy Effectiveness in Feedback Nash LQ-Games

Directory of Open Access Journals (Sweden)

Nicola Acocella

2008-12-01

Full Text Available This paper illustrates how the classical theory of economic policy can profitably be used to verify some properties of the Linear Nash Feedback Equilibrium in difference LQ-games. In particular, we find that both a necessary condition for the equilibrium existence and a sufficient condition for policy ineffectiveness can be defined in the terms of the simple Tinbergen counting rule.

The Optimal Nash Equilibrium Strategies Under Competition

Institute of Scientific and Technical Information of China (English)

孟力; 王崇喜; 汪定伟; 张爱玲

2004-01-01

This paper presented a game theoretic model to study the competition for a single investment oppertunity under uncertainty. It models the hazard rate of investment as a function of competitors' trigger level. Under uncertainty and different information structure, the option and game theory was applied to researching the optimal Nash equilibrium strategies of one or more firm. By means of Matlab software, the paper simulates a real estate developing project example and illustrates how parameter affects investment strategies. The paper's work will contribute to the present investment practice in China.

Kinetic study on ligand exchange reaction between ethylenedicysteine and 99mTc- glucoheptonate (99mTc-GH)

International Nuclear Information System (INIS)

Wu, C.Y.; Ji, S.R.; Lu, C.X.; Ding, S.Y.; Chen, Z.P.; Lin, X.T.

2002-01-01

Aim: 99m Tc-L,L-ethylenedicysteine( 99m Tc-EC)is a new type of renal imaging agent. It can be labeled very easily and efficiently at room temperature through direct labeling at pH 12. The need for direct labeling at pH 12 does not compromise the simplicity and ease of preparation of 99m Tc-EC and its practical usefulness in daily routine. On the basis of the labeling experiments, we developed a ligand exchange labeling method, in which the labeling EC with 99m Tc can be performed at pH 8. In order to provide a theoretic basis, a detailed kinetic study of ligand exchange reaction between 99m Tc- glucoheptonate( 99m Tc-GH) and EC was carried out. Materials and Methods: 99m Tc-EC is prepared as follows: 99m Tc-GH + EC → 99m Tc-EC + GH, labeling can be easily performed by adding 99m TcO 4 - (2∼6ml generator elute) to glucoheptonate solution containing SnCl 2 .2H 2 O solution to form 99m Tc-GH, then freshly prepared 99m Tc-GH is transferred to the aqueous solution of different concentrations of EC at different pH value, after being shaken, 99m Tc-EC was formed. Radiolabeling yield(RLY) and radiochemical purity(RCP) of 99m Tc-GH and 99m Tc-EC were measured by Xinhua No.1 paper with developing system of Me 2 CO/H 2 O/con.NH 3 .H 2 O=9/3/1(V/V). 99m Tc-GH(RCP must be over 98%, 80ul, 3.6∼7.4MBq) was added to 1ml of 0.5mol/L phosphate buffer(pH 12) containing different amount of EC(150, 75, 50 and 15ug), the sample was taken out at different time intervals and RCP was determined. The solution of EC(30ul, 5g/L) was added to 1ml of 0.5mol/L phosphate buffer at different pH value(pH11, 10, 9, 8, 7), after completely vortexed, 99m Tc-GH(RCP must be over 98%, 80ul, 3.6∼7.4MBq) was then added, the sample was taken out and RCP was determined as above. The rate constant(k) of ligand exchange reaction at different concentrations of EC and different reaction pH values were calculated out by integrating. Plot ln[1/(1-RLY)] vs t(time) showed a liner relationship, and the rate

Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) inhibits experimental choroidal neovascularization in vivo and VEGF-induced cell migration and tube formation in vitro.

Science.gov (United States)

Lai, Kunbei; Xu, Li; Jin, Chenjin; Wu, Kaili; Tian, Zhen; Huang, Chuangxin; Zhong, Xiaojing; Ye, Haiyun

2011-07-29

To investigate the effects of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of choroidal neovascularization (CNV), together with its underlying mechanisms. C57BL/6J mice were used to induce CNV by laser photocoagulation. (99)Tc-MDP at the doses of 0.5 × 10(-1), 1 × 10(-1), and 2 × 10(-1) μg/kg or the same volume of PBS was intraperitoneally injected daily after photocoagulation until the end of the experiment. Seven days after laser injury, mice were perfused with fluorescein-labeled dextran, and areas of CNV were measured. Numbers of infiltrating macrophages, protein levels of VEGF, and inflammation-related molecules including intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-α, and matrix metalloproteinases (MMPs) in the RPE-choroid complex were detected 3 days after laser photocoagulation. Effects of (99)Tc-MDP on VEGF-induced endothelial cell migration and tube formation were also studied. Toxicity of (99)Tc-MDP was evaluated in vivo and in vitro. Areas of CNV were significantly suppressed by (99)Tc-MDP treatment without toxicity to the retina compared with PBS treatment in a dose-dependent manner: (99)Tc-MDP treatment of 0.5 × 10(-1) μg/kg (5698.60 ± 1037.70 μm(2)), 1 × 10(-1) μg/kg (3678.34 ± 1328.18 μm(2)), and 2 × 10(-1) μg/kg (2365.78 ± 923.80 μm(2)) suppressed the development of CNV by 36.12%, 58.76%, and 73.48%, respectively, compared with that in the PBS treatment group (8920.36 ± 1097.29 μm(2); P 99)Tc-MDP treatment led to significant inhibition of macrophages infiltrating to CNV together with downregulated protein expressions of VEGF, ICAM-1, TNF-α, and MMP-2. (99)Tc-MDP also showed an inhibitive effect on cell proliferation and VEGF-induced migration and capillary-like tube formation of endothelial cells. Anti-inflammatory treatment with (99)Tc-MDP has therapeutic potential for CNV-related diseases.

Motion – All Patients with NASH Need to Have a Liver Biopsy: Arguments for the Motion

Directory of Open Access Journals (Sweden)

Jayant A Talwalkar

2002-01-01

Full Text Available Previously regarded as an obscure disorder, nonalcoholic steatohepatitis (NASH has recently emerged as an important chronic liver disease. NASH is within a spectrum of disorders characterized by excessive accumulation of fat in the liver, including simple hepatic steatosis (fatty liver, inflammation and necrosis (steatohepatitis, and fibrosis. Collectively, the disorders are called nonalcoholic fatty liver disease (NAFLD. Estimates of the prevalence of these individual conditions are suspect because liver biopsy is required for definitive diagnosis and is not generally performed. Although these conditions have traditionally been thought of as diseases of obese women, and are frequently associated with diabetes mellitus and hypertriglyceridemia, they have also been identified in lean men. Insulin resistance appears to be a common factor. These conditions are difficult to distinguish from each other clinically, and no biochemical or radiological test reliably establishes the diagnosis. A ratio of serum aspartate to alanine aminotransferase levels of less than one can distinguish NAFLD from alcoholic liver disease, but this is a nonspecific finding. Fatty infiltration imparts a diffuse echogenicity to the liver at ultrasonography, but this test cannot easily distinguish fat from fibrous tissue or identify cases of NASH. Only histological examination can establish the diagnosis of NASH, grade its severity, determine the prognosis and guide treatment.

Effects of subinhibitory concentrations of antimicrobial agents on Escherichia coli O157:H7 Shiga toxin release and role of the SOS response.

Science.gov (United States)

Nassar, Farah J; Rahal, Elias A; Sabra, Ahmad; Matar, Ghassan M

2013-09-01

Treatment of Escherichia coli O157:H7 by certain antimicrobial agents often exacerbates the patient's condition by increasing either the release of preformed Shiga toxins (Stx) upon cell lysis or their production through the SOS response-triggered induction of Stx-producing prophages. Recommended subinhibitory concentrations (sub-MICs) of azithromycin (AZI), gentamicin (GEN), imipenem (IMI), and rifampicin (RIF) were evaluated in comparison to norfloxacin (NOR), an SOS-inducer, to assess the role of the SOS response in Stx release. Relative expression of recA (SOS-inducer), Q (late antitermination gene of Stx-producing prophage), stx1, and stx2 genes was assessed at two sub-MICs of the antimicrobials for two different strains of E. coli O157:H7 using reverse transcription-real-time polymerase chain reaction. Both strains at the two sub-MICs were also subjected to Western blotting for LexA protein expression and to reverse passive latex agglutination for Stx detection. For both strains at both sub-MICs, NOR and AZI caused SOS-induced Stx production (high recA, Q, and stx2 gene expression and high Stx2 production), so they should be avoided in E. coli O157:H7 treatment; however, sub-MICs of RIF and IMI induced Stx2 production in an SOS-independent manner except for one strain at the first twofold dilution below MIC of RIF where Stx2 production decreased. Moreover, GEN caused somewhat increased Stx2 production due to its mode of action rather than any effect on gene expression. The choice of antimicrobial therapy should rely on the antimicrobial mode of action, its concentration, and on the nature of the strain.

On Nash Equilibrium and Evolutionarily Stable States That Are Not Characterised by the Folk Theorem.

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Jiawei Li

Full Text Available In evolutionary game theory, evolutionarily stable states are characterised by the folk theorem because exact solutions to the replicator equation are difficult to obtain. It is generally assumed that the folk theorem, which is the fundamental theory for non-cooperative games, defines all Nash equilibria in infinitely repeated games. Here, we prove that Nash equilibria that are not characterised by the folk theorem do exist. By adopting specific reactive strategies, a group of players can be better off by coordinating their actions in repeated games. We call it a type-k equilibrium when a group of k players coordinate their actions and they have no incentive to deviate from their strategies simultaneously. The existence and stability of the type-k equilibrium in general games is discussed. This study shows that the sets of Nash equilibria and evolutionarily stable states have greater cardinality than classic game theory has predicted in many repeated games.

On Nash Equilibrium and Evolutionarily Stable States That Are Not Characterised by the Folk Theorem

Science.gov (United States)

Li, Jiawei; Kendall, Graham

2015-01-01

In evolutionary game theory, evolutionarily stable states are characterised by the folk theorem because exact solutions to the replicator equation are difficult to obtain. It is generally assumed that the folk theorem, which is the fundamental theory for non-cooperative games, defines all Nash equilibria in infinitely repeated games. Here, we prove that Nash equilibria that are not characterised by the folk theorem do exist. By adopting specific reactive strategies, a group of players can be better off by coordinating their actions in repeated games. We call it a type-k equilibrium when a group of k players coordinate their actions and they have no incentive to deviate from their strategies simultaneously. The existence and stability of the type-k equilibrium in general games is discussed. This study shows that the sets of Nash equilibria and evolutionarily stable states have greater cardinality than classic game theory has predicted in many repeated games. PMID:26288088

Statins improve NASH via inhibition of RhoA and Ras

DEFF Research Database (Denmark)

Schierwagen, Robert; Maybüchen, Lara; Hittatiya, Kanishka

2016-01-01

. Hepatic steatosis, inflammation, and fibrosis were assessed by histology, Western blot, and RT-PCR measurements of cholesterol and hydroxyproline content. SMV treatment significantly decreased hepatic inflammation and fibrosis, but had no significant effect on steatosis and hepatic cholesterol content...... by statins is responsible for the beneficial hepatic effects in NASH....

Mapping Modular SOS to Rewriting Logic

DEFF Research Database (Denmark)

Braga, Christiano de Oliveira; Haeusler, Edward Hermann; Meseguer, José

2003-01-01

and verification of MSOS specifications, we have defined a mapping, named , from MSOS to rewriting logic (RWL), a logic which has been proposed as a logical and semantic framework. We have proven the correctness of and implemented it as a prototype, the MSOS-SL Interpreter, in the Maude system, a high......Modular SOS (MSOS) is a framework created to improve the modularity of structural operational semantics specifications, a formalism frequently used in the fields of programming languages semantics and process algebras. With the objective of defining formal tools to support the execution...

SOS: Observation, Intervention, and Scaffolding towards Successful Online Students

Science.gov (United States)

Ainsa, Trisha

2017-01-01

Research, reflection, and evaluation of online classes indicated a need for graduated scaffolding for first time students experiencing distance learning. In order to promote student engagement in the online learning process, I designed SOS for beginning online students. Sixty-three online students were offered an opportunity to participate in a…

Placental extract ameliorates non-alcoholic steatohepatitis (NASH by exerting protective effects on endothelial cells

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Akihiro Yamauchi

2017-09-01

Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the HPE-treated mice. Levels of TNF-α and MMP9 expression were also significantly reduced in HPE-treated mice, and oxidative stress was suppressed in the perivascular region. In addition, HPE dose-dependently increased survival of cultured endothelial cells exposed to 100 μM H2O2, and it upregulated expression of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations, we conclude that HPE ameliorates NASH-associated pathologies by suppressing inflammation, oxidative stress and fibrosis. These beneficially effects of HPE are in part attributable to its protective effects on liver sinusoidal endothelial cells. HPE could thus be an attractive therapeutic candidate with which to suppress progression from simple fatty liver to NASH.

Labeling and stability of radiolabeled antibody fragments by a direct 99mTc-labeling method

International Nuclear Information System (INIS)

Pak, K.Y.; Nedelman, M.A.; Tam, S.H.; Wilson, E.; Daddona, P.E.

1992-01-01

The in vitro labeling and stability of 99m Tc-labeled antibody Fab' fragments prepared by a direct labeling technique were evaluated. Eight antibody fragments derived from murine IgG1 (N = 5), IgG2a (N = 2) and IgG3 (N = 1) isotypes were labeled with a preformed 99m Tc-D-glucarate complex. No loss of radioactivity incorporation was observed for all the 99m Tc-labeled antibody fragments after 24 h incubation at 37 o C. 99m Tc-labeled antibody fragments (IgG1, N = 2; IgG2a, n = 2; IgG3, N = 1) were stable upon challenge with DTPA, EDTA or acidic pH. Using the affinity chromatography technique, two of the 99m Tc-labeled antibody fragments displayed no loss of immunoreactivity after prolonged incubation in phosphate buffer up to 24 h at 37 o C. Bonding between 99m Tc and antibody fragments was elucidated by challenging with a diamide ditholate (N 2 S 2 ) compound. The Fab' with IgG2a isotype displayed tighter binding to 99m Tc in comparison to Fab' from IgG1 and IgG3 isotype in N 2 S 2 challenge and incubation with human plasma. The in vivo biodistribution of five 99m Tc-labeled fragments were evaluated in normal mice. (Author)

Comparative biological evaluation between 99mTc tricarbonyl and 99mTc-Sn(II) levosalbutamol as a β2-adrenoceptor agonist

International Nuclear Information System (INIS)

Sanad, Mahmoud H.; Borai, Emad H.

2015-01-01

This study describes the comparison between 99m Tc-tricarbonyl and 99m Tc-Sn (II) levosalbutamol as a β 2 -adrenoceptors radiopharmaceutical and evaluation of their different biological characteristics using experimental animals. Levosalbutamol was labeled firstly with 99m Tc in the presence of SnCl 2 . 2H 2 O as a reducing agent under the optimum conditions: pH 8, 50 μg SnCl 2 . 2H 2 O, room temperature, 40 μg levosalbutamol and 30 min reaction time to give a maximum radiochemical yield of 98 ± 0.1%. The obtained 99m Tc-levosalbutamol was stable for a time up to 8 h. Secondly, 99m Tc-tricarbonyl ([ 99m Tc(CO) 3 (H 2 O) 3 ] + ) levosalbutamol was prepare under 30 min heating at 100 C. Labeling yield and stability were analyzed by high performance liquid chromatography (labeling yield >99% and stability for 8 h). Biodistribution investigation showed that, the maximum uptake ratio of the 99m Tc-levosalbutamol ( 99m Tc-Lev) between lung and heart was 2.34 ± 0.62 % of the injected activity/g tissue organ, at 30 min post-injection. But in case of 99m Tc-tricarbonyl levosalbutamol ( 99m Tc-tricarbonyl Lev) the maximum uptake ratio was 3.6 ± 0.11 of the injected activity/g tissue organ, at 30 min post-injection. This indicates that 99m Tc-tricarbonyl levosalbutamol was more selective for lung β 2 -adrenoceptors than 99m Tc-levosalbutamol. These results introduce 99m Tc-tricarbonyl levosalbutamol as a novel potential radiopharmaceutical for lung imaging.

Midkine Increases Diagnostic Yield in AFP Negative and NASH-Related Hepatocellular Carcinoma.

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Roslyn Vongsuvanh

Full Text Available Robust biomarkers for population-level hepatocellular carcinoma (HCC surveillance are lacking. We compared serum midkine (MDK, dickkopf-1 (DKK1, osteopontin (OPN and AFP for HCC diagnosis in 86 HCC patients matched to 86 cirrhotics, 86 with chronic liver disease (CLD and 86 healthy controls (HC. Based on the performance of each biomarker, we assessed a separate longitudinal cohort of 28 HCC patients, at and before cancer diagnosis. Serum levels of MDK and OPN were higher in HCC patients compared to cirrhosis, CLD and HC groups. DKK1 was not different between cases and controls. More than half of HCC patients had normal AFP. In this AFP-negative HCC cohort, 59.18% (n = 29/49 had elevated MDK, applying the optimal cut-off of 0.44 ng/ml. Using AFP ≥ 20 IU/ml or MDK ≥ 0.44 ng/ml, a significantly greater number (76.7%; n = 66/86 of HCC cases were detected. The area under the receiver operating curve for MDK was superior to AFP and OPN in NASH-HCC diagnosis. In the longitudinal cohort, MDK was elevated in 15/28 (54% of HCC patients at diagnosis, of whom 67% had elevated MDK 6 months prior.AFP and MDK have a complementary role in HCC detection. MDK increases the diagnostic yield in AFP-negative HCC and has greater diagnostic performance than AFP, OPN and DKK-1 in the diagnosis of NASH-HCC. Additionally, MDK has a promising role in the pre-clinical diagnosis of HCC.

On Cournot-Nash-Walras Equilibria and Their Computation

Czech Academy of Sciences Publication Activity Database

Outrata, Jiří; Ferris, M.C.; Červinka, Michal; Outrata, M.

2016-01-01

Roč. 24, č. 3 (2016), s. 387-402 ISSN 1877-0533 R&D Projects: GA ČR GAP402/12/1309; GA ČR GA15-00735S Grant - others:GA UK(CZ) SFG 2567; Australian Research Council(AU) DP-110102011 Institutional support: RVO:67985556 Keywords : Cournot-Nash-Walras equilibrium * Existence * Stationarity conditions * Stability * MOPEC Subject RIV: BA - General Mathematics Impact factor: 0.886, year: 2016 http://library.utia.cas.cz/separaty/2016/MTR/outrata-0460895.pdf

Lex marks the spot: the virulent side of SOS and a closer look at the LexA regulon.

Science.gov (United States)

Kelley, William L

2006-12-01

The SOS response that responds to DNA damage induces many genes that are under LexA repression. A detailed examination of LexA regulons using genome-wide techniques has recently been undertaken in both Escherichia coli and Bacillus subtilis. These extensive and elegant studies have now charted the extent of the LexA regulons, uncovered many new genes, and exposed a limited overlap in the LexA regulon between the two bacteria. As more bacterial genomes are analysed, more curiosities in LexA regulons arise. Several notable examples include the discovery of a LexA-like protein, HdiR, in Lactococcus lactis, organisms with two lexA genes, and small DNA damage-inducible cassettes under LexA control. In the cyanobacterium Synechocystis, genetic and microarray studies demonstrated that a LexA paralogue exerts control over an entirely different set of carbon-controlled genes and is crucial to cells facing carbon starvation. An examination of SOS induction evoked by common therapeutic drugs has shed new light on unsuspected consequences of drug exposure. Certain antibiotics, most notably fluoroquinolones such as ciprofloxacin, can induce an SOS response and can modulate the spread of virulence factors and drug resistance. SOS induction by beta-lactams in E. coli triggers a novel form of antibiotic defence that involves cell wall stress and signal transduction by the DpiAB two-component system. In this review, we provide an overview of these new directions in SOS and LexA research with emphasis on a few themes: identification of genes under LexA control, the identification of new endogenous triggers, and antibiotic-induced SOS response and its consequences.

The clinical use of myocardial gated SPECT imaging with 99TcmN-NOEt

International Nuclear Information System (INIS)

Li Sijin; Hu Guang; Liu Jianzhong; Tian Mei; Li Xianfeng; Zhang Wanchun; Wang Jin

2002-01-01

Objective: To evaluate the clinical value of 99 Tc m N-NOEt myocardial perfusion imaging comparing with 99 Tc m -MIBI. Methods: Twenty patients (pts) were divided into 2 groups. Group 1 (G1), left ventricular ejection fraction (LVEF) ≥ 50%, 13 pts, the mean age was (49.9 +- 14.7) years. Group 2 (G2), LVEF 0.05 vs G1). All the pst underwent gated SPECT imaging at 30 and 120 min after injection of 925 MBq 99 Tc m N-NOEt at rest, and the heart to lung (H/L) activity ratio was calculated. Of the 6 pts in G2 and 1 pt in G1 underwent the 99 Tc m -MIBI imaging within 3 days to the former imaging at 120 min after 99 Tc m -MIBI injection under the same condition as at 99 Tc m N-NOEt imaging. The left ventricles of the 7 pts were divided into 63 segments with 9 segments for each, and the four-point scoring system was used to evaluate the tracer uptake in the segments. Results: The H/L ratio was 1.47 +- 0.47 and 1.59 +- 0.53 (P > 0.50) respectively in G1 and was 0.72 +- 0.11 and 0.89 +- 0.11 (P 99 Tc m N-NOEt and 99 Tc m -MIBI for the presence of defects was 93.65%, Kappa +- s = 0.87 +- 0.12. The mean score was 2.0 +- 0.84 (MIBI) and 2.38 +- 0.84 (NOEt) respectively (P > 0.05). Conclusions: 1) If the lung uptake of 99 Tc m N-NOET showed higher, it suggested that the left ventricular function was poor. 2) The results of LVEF, EDV and ESV were accordant between MIBI and NOEt. 3) The extent and intensity of myocardial defect with NOEt imaging was more severe than that with MIBI

The recX gene product is involved in the SOS response in Herbaspirillum seropedicae

International Nuclear Information System (INIS)

Galvao, C.W.; Pedrosa, F.O.; Souza, E.M.; Yates, M.G.; Chubatsu, L.S.; Steffens, M.B.R.

2003-01-01

The recA and the recX genes of Herbaspirillum seropedicae were sequenced. The recX is located 359 bp downstream from recA. Sequence analysis indicated the presence of a putative operator site overlapping a probable σ 70 -dependent promoter upstream of recA and a transcription terminator downstream from recX, with no apparent promoter sequence in the intergenic region. Transcriptional analysis using lacZ promoter fusions indicated that recA expression increased three- to fourfold in the presence of methyl methanesulfonate (MMS). The roles of recA and recX genes in the SOS response were determined from studies of chromosomal mutants. The recA mutant showed the highest sensitivity to MMS and UV, and the recX mutant had an intermediate sensitivity, compared with the wild type (SMR1), confirming the essential role of the RecA protein in cell viability in the presence of mutagenic agents and also indicating a role for RecX in the SOS response. (author)

The recX gene product is involved in the SOS response in Herbaspirillum seropedicae

Energy Technology Data Exchange (ETDEWEB)

Galvao, C.W.; Pedrosa, F.O.; Souza, E.M.; Yates, M.G.; Chubatsu, L.S.; Steffens, M.B.R. [Univ. Federal do Parana, Dept. of Biochemistry and Molecular Biology, Curitiba (Brazil)]. E-mail: steffens@bioufpr.br

2003-02-15

The recA and the recX genes of Herbaspirillum seropedicae were sequenced. The recX is located 359 bp downstream from recA. Sequence analysis indicated the presence of a putative operator site overlapping a probable {sigma}{sup 70}-dependent promoter upstream of recA and a transcription terminator downstream from recX, with no apparent promoter sequence in the intergenic region. Transcriptional analysis using lacZ promoter fusions indicated that recA expression increased three- to fourfold in the presence of methyl methanesulfonate (MMS). The roles of recA and recX genes in the SOS response were determined from studies of chromosomal mutants. The recA mutant showed the highest sensitivity to MMS and UV, and the recX mutant had an intermediate sensitivity, compared with the wild type (SMR1), confirming the essential role of the RecA protein in cell viability in the presence of mutagenic agents and also indicating a role for RecX in the SOS response. (author)

The recX gene product is involved in the SOS response in Herbaspirillum seropedicae.

Science.gov (United States)

Galvão, Carolina W; Pedrosa, Fábio O; Souza, Emanuel M; Yates, M Geoffrey; Chubatsu, Leda S; Steffens, Maria Berenice R

2003-02-01

The recA and the recX genes of Herbaspirillum seropedicae were sequenced. The recX is located 359 bp downstream from recA. Sequence analysis indicated the presence of a putative operator site overlapping a probable sigma70-dependent promoter upstream of recA and a transcription terminator downstream from recX, with no apparent promoter sequence in the intergenic region. Transcriptional analysis using lacZ promoter fusions indicated that recA expression increased three- to fourfold in the presence of methyl methanesulfonate (MMS). The roles of recA and recX genes in the SOS response were determined from studies of chromosomal mutants. The recA mutant showed the highest sensitivity to MMS and UV, and the recX mutant had an intermediate sensitivity, compared with the wild type (SMR1), confirming the essential role of the RecA protein in cell viability in the presence of mutagenic agents and also indicating a role for RecX in the SOS response.

Cytokeratin 18 as a non invasive marker in diagnosis of NASH and ...

African Journals Online (AJOL)

Mohsen M. Maher

2014-12-19

Dec 19, 2014 ... diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian ... International Business Machines; IR, insulin resistance; LDL, low ..... Logistic Regression Test showing positive prediction of. CK18 in ...

99Mo-99mTc generator - study of their performance and quality

International Nuclear Information System (INIS)

Acar, M.E.D.

1987-01-01

In this work the performance of the 99 Mo - 99m Tc generators produced at IPEN-CNEN/SP as well as the quality of the eluted solutions were analysed. The following parameters were studied: elution efficiency, chemical radiochemical, radionuclidic and microbiological purities and pH of the eluates. The 99m Tc yield ranged from 84,7 to 98,5%. The radioactivity due to the pertechnetate ion in the studied solutions was higher than 97,5%. The aluminium content in eluates, determined by spectrophotometry, was lower than 2,5 μg/ml and the pH of the solutions between 4,5 and 5,1. Radioactive impurities of the order of 10 -3 KBq 99 Mc/MBq 99m Tc and 10 -5 KBq 131 I/MBq 99m Tc were found in the eluates at the time of elution. Other γ emitting radioactive impurities were order of 10 -3 KBq/MBq 99m Tc. The eluates were sterile and pyrogen-free. From the results obtained in this work one can state that the IPEN-TEC generator is a reliable source of good quality 99m Tc-pertechnetate. (author) [pt

Remediating Language Deficient/Dyslexic College Students: An Interview with Robert Nash.

Science.gov (United States)

Lundquist, Arlene J.; Nash, Robert

1988-01-01

Robert Nash responds to questions concerning his personal and professional background, the Simultaneous Multisensory Instructional Procedure for Teaching the Complete Sound Structure of the Language, problems associated with dyslexia, the social/emotional impact of learning disabilities, and the University of Wisconsin's Project Success for…

77 FR 10553 - Match-E-Be-Nash-She-Wish Band of Pottawatomi Indians (Gun Lake)-Amendment to Liquor Beverage...

Science.gov (United States)

2012-02-22

... DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs Match-E-Be-Nash-She-Wish Band of Pottawatomi Indians (Gun Lake)-- Amendment to Liquor Beverage Control Ordinance AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice SUMMARY: This notice publishes the amendments to the Match-E-Be-Nash- She-Wish...

Starvation, Together with the SOS Response, Mediates High Biofilm-Specific Tolerance to the Fluoroquinolone Ofloxacin

Science.gov (United States)

Bernier, Steve P.; Lebeaux, David; DeFrancesco, Alicia S.; Valomon, Amandine; Soubigou, Guillaume; Coppée, Jean-Yves; Ghigo, Jean-Marc; Beloin, Christophe

2013-01-01

High levels of antibiotic tolerance are a hallmark of bacterial biofilms. In contrast to well-characterized inherited antibiotic resistance, molecular mechanisms leading to reversible and transient antibiotic tolerance displayed by biofilm bacteria are still poorly understood. The physiological heterogeneity of biofilms influences the formation of transient specialized subpopulations that may be more tolerant to antibiotics. In this study, we used random transposon mutagenesis to identify biofilm-specific tolerant mutants normally exhibited by subpopulations located in specialized niches of heterogeneous biofilms. Using Escherichia coli as a model organism, we demonstrated, through identification of amino acid auxotroph mutants, that starved biofilms exhibited significantly greater tolerance towards fluoroquinolone ofloxacin than their planktonic counterparts. We demonstrated that the biofilm-associated tolerance to ofloxacin was fully dependent on a functional SOS response upon starvation to both amino acids and carbon source and partially dependent on the stringent response upon leucine starvation. However, the biofilm-specific ofloxacin increased tolerance did not involve any of the SOS-induced toxin–antitoxin systems previously associated with formation of highly tolerant persisters. We further demonstrated that ofloxacin tolerance was induced as a function of biofilm age, which was dependent on the SOS response. Our results therefore show that the SOS stress response induced in heterogeneous and nutrient-deprived biofilm microenvironments is a molecular mechanism leading to biofilm-specific high tolerance to the fluoroquinolone ofloxacin. PMID:23300476

A methionine-choline-deficient diet elicits NASH in the immunodeficient mouse featuring a model for hepatic cell transplantation.

Science.gov (United States)

Pelz, Sandra; Stock, Peggy; Brückner, Sandra; Christ, Bruno

2012-02-01

Non-alcoholic staetohepatitis (NASH) is associated with fat deposition in the liver favoring inflammatory processes and development of fibrosis, cirrhosis and finally hepatocellular cancer. In Western lifestyle countries, NASH has reached a 20% prevalence in the obese population with escalating tendency in the future. Very often, liver transplantation is the only therapeutic option. Recently, transplantation of hepatocyte-like cells differentiated from mesenchymal stem cells was suggested a feasible alternative to whole organ transplantation to ameliorate donor organ shortage. Hence, in the present work an animal model of NASH was established in immunodeficient mice to investigate the feasibility of human stem cell-derived hepatocyte-like cell transplantation. NASH was induced by feeding a methionine/choline-deficient diet (MCD-diet) for up to 5 weeks. Animals developed a fatty liver featuring fibrosis and elevation of the proinflammatory markers serum amyloid A (SAA) and tumor necrosis factor alpha (TNFα). Hepatic triglycerides were significantly increased as well as alanine aminotransferase demonstrating inflammation-linked hepatocyte damage. Elevation of αSMA mRNA and collagen I as well as liver architecture deterioation indicated massive fibrosis. Both short- and long-term post-transplantation human hepatocyte-like cells resided in the mouse host liver indicating parenchymal penetration and most likely functional engraftment. Hence, the NASH model in the immunodeficient mouse is the first to allow for the assessment of the therapeutic impact of human stem cell-derived hepatocyte transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.

Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice.

Science.gov (United States)

Honda, Takashi; Ishigami, Masatoshi; Luo, Fangqiong; Lingyun, Ma; Ishizu, Yoji; Kuzuya, Teiji; Hayashi, Kazuhiko; Nakano, Isao; Ishikawa, Tetsuya; Feng, Guo-Gang; Katano, Yoshiaki; Kohama, Tomoya; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Goto, Hidemi; Hirooka, Yoshiki

2017-04-01

For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis. In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH. Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation. Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (PBCAA was significantly lower than those of CDHF-control. BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Technetium-99m pertechnetate - a tracer for radiolabelling antibody for inflammation detection

International Nuclear Information System (INIS)

Shaharuddin Mohd; Wan Hamirul Bahrin Wan Kamal; Shahrin A Hamid; Ang Woan Tze; Rosnani Hashim

1999-01-01

The polyclonal antibody, Human Immunoglobulin G (HlgG) was reduced by using 2-mercaptoethanol with molar ratio of 1000:1 (i.e. mercaptoethanol:antibody). The reduction of the antibody, was carried out for 30 minutes at room temperature. The reduced antibody was purified by using Sephadex G-25 fine column. The antibody kit for the detection of inflammation was prepared aseptically in Class 1 Laminar Flow cabinet. The kit passed the sterility test. Upon reconstitution of the antibody kit with sodium pertechnetate-99m ( 99m Tc) solution, the labelling efficiency obtained was more than 95%. This preparation was stable up to 24-hour stored at room temperature. Gamma camera scans showed the accumulation of technetium-99m labelled antibody ( 99m Tc-HIgG) at the turpentine-induced inflammation of female Sprague-Dawley rats. This indicated the possibility of using 99m Tc-HIgG for inflammation detection. (author)

The Use of Sodium Hypochlorite Solution for (n,γ99Mo/99mTc Generator Based on Zirconium-Based Material (ZBM

Directory of Open Access Journals (Sweden)

I. Saptiama

2015-08-01

Full Text Available The many problems in preparing fission product 99Mo led into this work to develop 99Mo/99mTc generator using neutron-irradiated natural MoO3 targets and, more specifically, to develop a zirconium-based material (ZBM for chromatography columns that have an adsorption capacity of more than 100 mg Mo/g ZBM. This paper reports our recent experiments in the use of sodium hypochlorite solution of various concentrations to improve the yield of 99mTc in performance of (n,γ99Mo/99mTc generators based on the ZBM. The synthesized ZBM was coated with tetraethyl orthosilicate for improving the hardness of the material. The adsorption of [99Mo]molybdate into ZBM was carried out by reacting ZBM into [99Mo]molybdate solution at 90°C to form ZBM-[99Mo] molybdate. ZBM-[99Mo]molybdate was then packed into generator column, then eluted with 10 × 1 mL of saline followed by 1 × 5 mL of NaOCl solution. The NaOCl solution concentrations used were 0.5%; 1%; 3%; and 5% for each column, respectively. This study resulted in a ZBM which has a 99Mo adsorption capacity of 167.5 ± 3.4 mgMo/g ZBM, as well as in a yield eluate of 99mTc of up to 70%, and the find that the optimum NaOCl concentration was 3%. The use of sodium hypochlorite solution affected 99Mo breakthrough. The higher sodium hypochlorite concentration used, the more 99Mo breaktrough exist on 99mTc eluate.

Final Report for DOE Project DE-FC07-99CH11010

Energy Technology Data Exchange (ETDEWEB)

Jed Randall; Robert Kean

2003-10-22

Department of Energy award number DE-FC07-99CH11010, Enhanced Utilization of Corn Based Biomaterials, supported a technology development program sponsored by Cargill Dow LLC from September 30, 1999 through June 30, 2003. The work involved fundamental scientific studies on poly lactic acid (PLA), a new environmentally benign plastic material from renewable resources. DOE funds supported academic research at the Colorado School of Mines and the National Renewable Energy Laboratory (NREL), and industry cost share was directed towards applied research into new product development utilizing the fundamental information generated by the academic partners. Under the arrangement of the grant, the fundamental information is published so that other companies can utilize it in evaluating the applicability of PLA in their own products. The overall project objective is to increase the utilization of PLA, a renewable resource based plastic, currently produced from fermented corn sugar.

Regulation of the E. coli SOS response by the lexA gene product

International Nuclear Information System (INIS)

Brent, R.

1983-01-01

In an Escherichia coli that is growing normally, transcription of many genes is repressed by the product of the lexA gene. If cellular DNA is damaged, proteolytically competent recA protein (recA protease) inactivates lexA protein and these genes are induced. Many of the cellular phenomena observed during the cellular response to DNA damage (the SOS response) are the consequence of the expression of these lexA-prepressed genes. Since the SOS response of E. coli has recently been the subject of a comprehensive review, in this paper I would like to concentrate on some modifications to the picture based on new data. 12 references, 2 figures

Preparation and characterization of iron(III) 99Mo-molybdate(VI) gels for the assessment of 99mTc elution performance

International Nuclear Information System (INIS)

Amin, Mahmoud; Fasih, Tharwat W.; El-Absy, Mohamed A.

2018-01-01

New iron(III) 99 Mo-molybdate(VI) gels (Fe 99 Mo) of high Mo content were prepared by the precipitation/filtration method. 99 Mo-MoO 3 dissolved in NaOH was added to aqueous solutions of Fe(NO 3 ) 3 at Mo/Fe mole fractions ∝2.21 and 1.99 with continuous stirring at ambient room temperature. Two different Fe 99 Mo were precipitated from the mixed solutions adjusted at pH 2 and 4.7. The amount of water of hydration increased with the increasing the gel settling time and pH of the mixed solution. The matrices were characterized by radiometric, XRD, SEM, XRF, FT-IR, TGA, and DTA measurements. Small chromatographic columns of 2.0 g Fe 99 Mo containing ≥800 mg Mo tagged with 740 MBq 99 Mo were eluted with 5 mL saline solution. Highly reproducible 99m Tc elution indices suitable for preparation of 99 Mo/ 99m Tc generators were achieved from generator supported with 0.5 g Al 2 O 3 filter. Elution performance of 99m Tc radionuclide was highly dependent on the gel structural properties.